The functional role of H1 and H2 receptors in mediating the effects of histamine on renal hemodynamics and tubular function was investigated in anesthetized dogs. Histamine, infused directly into the renal artery, caused decreases in renal vascular resistance and increases in total renal blood flow without significant changes in mean arterial blood pressure or glomerular filtration rate. These hemodynamic effects of histamine were inhibited by the H2-receptor antagonist, cimetidine, but not by the H1-receptor antagonist, tripelennamine. Histamine also caused increases in fractional urine flow and the fractional excretion of sodium and calcium with a concomitant decrease in urine/plasma osmolality. These tubular effects of histamine were antagonized by both tripelennamine and cimetidine. Histamine-induced increases in the fractional excretion of potassium were blocked only by tripelennamine. These results suggest that (1) both H1 and H2 receptors mediate the effects of histamine on urinary dilution and tubular reabsorption; (2) H2 receptors mediate the effects of histamine on renal hemodynamics, indicating that H2 receptors are present in the renal vasculature, and (3) H1 receptors may exist in the renal tubules.