The unique morphology of the juxtaglomerular complex has resulted in many investigations evaluating its potential physiological roles. One hypothesis that has stimulated considerable interest is that feedback signals originating from distal tubule cells, presumably at the macula densa segment, participate in the phenomenon of renal autoregulation. Data obtained from dog experiments indicate tha autoregulation of single nephron glomerular filtration rate (SNGFR) is most consistently observed when fluid delivery to the early distal tubule is not interrupted. In contrast, techniques that interfere with normal orthograde fluid delivery to the distal nephron have usually resulted in increases in SNGFR and an inability to exhibit appropriate autoregulatory responses to decreases in arterial pressure. There is considerable uncertainty concerning the nature of the intraluminal component of the early distal tubule fluid responsible for initiating feedback responses. The studies reported in this paper have indicated that feedback mediated decreases in stop-flow pressure and SNGFR in response to increases in distal microperfusion rate can occur with a variety of artificial perfusion solutions, including solutions that contain low concentrations of chloride, sodium, or total electrolytes. Microperfusion studies in the rat have demonstrated that feedback mediated decreases in stop-flow pressure can occur in the absence of associated increases in distal tubule fluid chloride concentration. These results are consistent with the concept that some function of distal tubule fluid osmolality or distal tubule solute delivery may participate in the initiation of feedback signals.