Within each nephron of the mammalian kidney, a feedback mechanism operating between the macula densa segment of the distal tubule and the afferent arteriole participates in the regulation of glomerular filtration rate. Retrograde microperfusion studies in rats were conducted to test the hypothesis that activation of macula densa cytoplasmic calcium is involved in the transmission of feedback signals to the vascular elements. Perfusion into distal tubules with a hypotonic solution (70 milliosmolar) elicited moderate decreases in glomerular pressure of 6 +/- 0.8 millimeters of mercury. With the addition of a calcium ionophore (A23187) glomerular pressure decreased by 16 +/- 1.1 millimeters of mercury. When a solution devoid of calcium but containing A23187 was used, the feedback response was inhibited. Thus, cytoplasmic calcium within the receptor cells may participate in the transmission of feedback signals to the contractile cells.