Baboons (Papio hamadryas) were infused intravenously with a nonhypotensive dose (0.1 microgram X min-1 X kg-1) of synthetic human atriopeptin III (ANF) for 60 min. Throughout the infusion in intact animals, ANF significantly increased glomerular filtration rate (GFR) (clearance of inulin) (P less than 0.001), and, to a lesser extent, total renal plasma flow (RPF) [clearance of p-aminohippurate (PAH)] (P less than 0.02) and filtration fraction (P less than 0.02). Concomitant increases in urinary flow rate and in the excretion of osmoles, sodium, chloride, potassium, phosphorus, and calcium were highly significant (less than 0.001 for all). To minimize the hemodynamic impact of ANF on GFR, the same dose of ANF was infused into the same animals 8 wk after uninephrectomy. Base-line single-kidney GFR was then 50% increased. With ANF infusion RPF increased significantly (P less than 0.02), as in intact baboons, but ANF then had only marginally significant effects on GFR (P = 0.06) and insignificant effects on filtration fraction (P = 0.17). Nevertheless, the changes in urinary flow rate and solute excretion rates were highly significant (P less than 0.001 to less than 0.007). In both groups, all changes developed rapidly, were sustained during the infusion of ANF, and were readily reversible within 15 to 30 min of cessation of ANF infusion. The data dissociate in uninephrectomized primate the effects of ANF on water and solute excretion from those on GFR and filtration fraction. Both in intact and in uninephrectomized baboons, the changes in water and solute excretion were associated with small but significant changes in RPF.