The renal effects of chlorpromazine (CPZ) were studied in sodium-loaded dogs. Intrarenal artery infusion of CPZ at 0.2 microM/kg/min induces a significant decrease of both clearance of PAH and GFR, with no measurable effect on the excretion of electrolytes. This result is interpreted as direct evidence in favor of a physiological role of dopamine, since CPZ is known to be a dopaminergic blocking agent. At 2.0 microM/kg/min, CPZ no longer induces a renal hemodynamic alteration, but has a powerful natriuretic effect associated with an increased kaliuresis, and an increase of the free water clearance; phosphate excretion was unchanged. This effect on the excretion of electrolytes is apparently reversible within the 30 minutes immediately following the discontinuation of the CPZ infusion. The CPZ-induced natriuresis and kaliuresis are not additive to aminophylline's, suggesting a renal cyclic nucleotide phosphodiesterase inhibition. In conclusion, CPZ has a dose-dependent effect on dog kidney: it induces a reduction of the renal hemodynamics at a low dose, and an inhibition of the tubular sodium transport at a high dose.