The effect of morphine or clonidine administered systemically on visceral and cutaneous spinal nociceptive transmission was examined in 45 dorsal horn neurons in spinalized, decerebrate rats: 17 'cutaneous' dorsal horn neurons located in the L3-L5 spinal segments were excited by heating the glabrous skin of the hindpaw (48°C, 15 s) and 28 'visceral' dorsal horn neurons located in the T13-L2 spinal segments were excited by colorectal distension (80 mmHg, 20 s). The 28 visceral dorsal horn neurons were subclassified as 18 short-latency abrupt neurons (SL-A), which were excited by colorectal distension at short latency (< 1 s) and whose activity abruptly returned to base line following termination of the distending stimulus, and as 10 short-latency sustained (SL-S) neurons, which also were excited at short latency (< 1 s) by colorectal distension, but whose activity was sustained above base line for 4-31 s following termination of the distending stimulus. Morphine produced a dose-dependent, naloxone-reversible inhibition of both spontaneous activity and/or neuronal responses during heating or colorectal distension of 8 SL-A, 7 SL-S, and 11 cutaneous dorsal horn neurons. Comparison of the effective doses of morphine to produce a 50% reduction in the response of the neurons (ED50s) during colorectal distension or heating demonstrated that, at the intensities of distension and heating employed, SL-S neurons were affected at the least dosage (ED50 = 0.46 μmol/kg), followed by SL-A neurons (ED50 = 1.95 μmol/kg) and cutaneous neurons (ED50 = 6.12 μmol/kg). Effects on spontaneous activity were variable: at low doses morphine produced an increase in the spontaneous activity of 2 SL-A and 5 cutaneous neurons; greater doses (up to 42 μmol/kg) inhibited in all of the SL-A and SL-S neurons, but not three cutaneous neurons studied. With the exclusion of these three neurons, the ED50s for inhibition of spontaneous activity were comparable to the ED50s for inhibition of neuronal responses during colorectal distension or heating of the hindpaw in all three neuronal groups. Clonidine produced a dose-dependent, yohimbine- or phentolamine-reversible inhibition of both spontaneous activity and neuronal responses during heating or colorectal distension of 10 SL-A, 3 SL-S, and 6 cutaneous dorsal horn neurons. Comparison of the ED50s of clonidine for inhibition of the response of the neurons during colorectal distension or heating demonstrated that, at the intensities of distension and heating employed, cutaneous neurons were affected at the least dosage (ED50 = 0.09 μmol/kg) and SL-A and SL-S neurons at greater dosages (grouped ED50 = 0.26 μmol/kg). In contrast to the effects of morphine, clonidine, at the doses employed, produced only inhibition of spontaneous activity; the ED50s for inhibition of spontaneous activity by clonidine were significantly lower than those for inhibition of responses during colorectal distension or heating of the hindpaw for all neuronal groups (cutaneous, 0.04 μmol/kg; SL-A, 0.05 μmol/kg; and SL-S, 0.09 μmol/kg). Morphine and clonidine had differential effects on the intensity coding of both visceral and cutaneous dorsal horn neurons. Morphine produced a rightward shift and significant reduction in the slope of linear stimulus-response functions (SRFs) relating neuronal responses to graded colorectal distension (20-100 mmHg, 20 s) or heating of the hindpaw (44-50°C, 15 s). Clonidine produced a parallel rightward shift in the SRFs without affecting the slope. The present data document quantitatively different inhibition of visceral and cutaneous spinal nociceptive transmission by morphine and clonidine. Although their effects on visceral and cutaneous spinal transmission are qualitatively similar (i.e., inhibitory), morphine and clonidine exhibited significantly different potencies against identical visceral or cutaneous stimuli and produced parametrically different effects on the intensity coding of spinal nociceptive transmission. It can be concluded that while morphine and clonidine may share some common mechanism(s) in the production of antinociception, there appear to be mechanisms operative which are unique to morphine.