The pressor, renal and endocrine effect of the physiological precursor of endothelial derived nitric oxide, L-arginine was compared, with a substrate inactive on nitric oxide, hypertonic D-glucose, in hypertensive patients. Ten mild-moderate essential hypertensives were assigned to either L-arginine (n = 5) or D-glucose (n = 5). Substances were infused over 25 min at equiosmolal rates preceded and followed by saline infusion for 25 min. Blood pressure and heart rate were monitored at 3-min intervals, while hormonal and humoral variables, inulin and paraaminohippurate clearance and electrolyte excretion were measured at the end of each period under conditions of maximal diuresis. L-arginine and D-glucose increased serum osmolality comparably and caused similar haemodilution to that with control saline. During L-arginine infusion, systolic and diastolic blood pressure decreased by 16.6% and 11%, respectively, and recovered in the postinfusion period. Heart rate, plasma renin activity, and plasma noradrenaline did not change significantly. The percent blood pressure decrement induced by L-arginine was significantly greater than that by D-glucose. Glomerular filtration rate was stable and renal plasma flow was increased by both substances. However, natriuresis, kaliuresis and chloruresis were markedly stimulated only by L-arginine, which also promoted the development of systemic acidosis, possibly as a consequence of hydrochloridric acid generated during its metabolism. Circulating insulin, atrial natriuretic peptide, growth hormone and glucagon levels were increased and plasma aldosterone was unchanged during infusion of L-arginine. Insulin was stimulated and the other hormones inhibited during infusion of D-glucose.(ABSTRACT TRUNCATED AT 250 WORDS)