The effect of growth hormone on tubular H+ secretion by the hypophysectomized and intact rat was studied in the isolated functioning kidney. Net acid secretion was estimated as the sum of HCO3- absorption plus NH+4 excretion. Kidneys from either intact or hypophysectomized rats were isolated and perfused over a 90-min time course during which either recombinant human growth hormone (GH), insulin-like growth factor-1 (IGF-1), porcine insulin, or vehicle was added; hormone response was then compared with the time controls. Compared with kidneys from intact rats, hypophysectomized rat kidneys exhibited a marked acidification defect, net H+ secretion, 13,530 +/- 600 vs. 17,860 +/- 810 (SE) nmol/ml of glomerular filtrate (GF). Administering GH (50 nM) increased net H+ secretion within 15 min in both hypophysectomized and intact groups to a maximum of 17,950 +/- 910 and 20,960 +/- 1,100 nmol/ml GF, respectively; neither insulin nor IGF-1 (50 nM) was able to mimic GH's effect. Addition of 1 mM amiloride completely abolished the GH-accelerated acid secretion and greater than 70% of the basal net acid secretion rate. Furthermore, GH-enhanced volume absorption was also abolished by amiloride, although neither NaCl nor glutamine absorption was affected. GH-accelerated acid secretion and coupled volume absorption could be observed at concentrations as low as 3.5 nM with half-maximal effect at 12 nM, which is within the range of GH concentration achieved during episodic GH surges. Finally administering GH in vivo to hypophysectomized rats enhanced net acid secretion and urinary acidification, consistent with accelerated tubular H+ secretion as one physiological expression of GH action.