PTH increases calcium reabsorption exclusively in the distal nephron. Two mechanisms of Ca++ transport through the basolateral membrane (BLM) have been described: the ATP-dependent and the sodium gradient-dependent transport. In the present study, we investigated the effect of PTH and (Bu)2cAMP on these two mechanisms. We recently reported, using 100 microM Ca++ as the substrate, that whereas the ATP-dependent system was present in the proximal and distal tubule (DCT), the Na+/Ca++ exchanger was located only in the DCT. Using 2 microM Ca++ as the substrate, the Na+/Ca++ exchanger was again found to be present only in the DCT. Incubation of DCT suspension with 10(-8) M bovine PTH (1-34) resulted in a significant increase in the Na(+)-dependent Ca++ uptake by the corresponding BLM vesicles. This effect was dose dependent. The half-maximal stimulation was obtained with 1 X 10(-8) M PTH. At this concentration, PTH increased the maximum velocity (Vmax) from 0.34 +/- 0.06 t 0.54 +/- 0.02 nmol/mg/10 s (P less than 0.05) without influencing the Michaelis-Menten constant (Kms). Incubation of DCT suspensions with (Bu)2cAMP mimicked this effect. The dose-response curve showed a peak action at 1 mM (Bu)2cAMP. In contrast, neither (Bu)2cAMP nor PTH influenced the ATP-dependent Ca++ transport through BLM from proximal tubule nor DCT. It is proposed that PTH influences Ca++ reabsorption by the DCT because the target molecule, the Na+/Ca++ exchanger, is located exclusively at this site.