To evaluate the contribution of chloride to the suppression of plasma renin activity (PRA) by KCl, PRA was measured before and after venous infusions of KCl, KHCO3, KNO3, and KC2H3O2 in dietary NaCl-restricted rats. In contrast to controls, PRA decreased (P less than 0.02) after infusion of each potassium salt [KCl from 55.3 +/- 6.4 to 27.0 +/- 6.4 ng.ml-1.h-1 (mean +/- SE); KC2H3O2 from 39.3 +/- 4.0 to 20.6 +/- 4.0; KHCO3 from 64.4 +/- 6.2 to 47.2 +/- 6.2; KNO3 from 40.0 +/- 4.0 to 18.6 +/- 4.0]. Arterial pressure, plasma volume, inulin clearance, serum sodium concentration, and net sodium balance were not different between control and potassium-infused groups. Potassium loading did not increase absolute or fractional sodium excretion. PRA failed to decrease in animals given an equal volume of NaNO3. Furosemide prevented the fall in PRA associated with potassium loading despite replacement of urinary losses. These results suggest that the decrease in PRA observed during potassium loading occurs through the macula densa mechanism but is not dependent on concomitant chloride administration. As furosemide prevents the fall in PRA, macula densa chloride transport may be necessary for potassium to exert this effect.