The vasoactive nucleoside adenosine has an important regulatory influence on most aspects of renal function in experimental animals. In this study, we evaluated the effects of intravenous adenosine on systemic and renal hemodynamics, tubular function, and plasma renin concentration in 10 healthy male subjects. Each of the subjects received two intravenous infusions of adenosine (70 micrograms.kg-1.min-1) and saline on three separate study days. There was no significant change in systemic blood pressure in response to adenosine, although there was a significant rise in heart rate postcommencement of adenosine (61.5 +/- 2.9 to 78.0 +/- 7.9 beats/min, 1 h postcommencement of adenosine on day 1, P < 0.01 vs. saline). There was a significant decline in 51Cr-EDTA clearance (glomerular filtration rate) (118.5 +/- 13.2 to 88.0 +/- 8.3 ml/min, P < 0.05 vs. saline) and filtration fraction (19.4 +/- 1.01 to 16.0 +/- 1.03%, P < 0.01 vs. saline) 1 h postcommencement of adenosine, although there was no significant change in 125I-hippuran clearance (effective renal plasma flow). Urine flow rate and osmolar and free water clearance decreased significantly in response to adenosine (particularly on study day 1). There was, in addition, a significant reduction in absolute and fractional excretion rates of sodium, lithium, phosphate, uric acid, chloride, and urea in response to adenosine. There was a rise in plasma renin concentration in response to adenosine, reaching levels of statistical significance on study day 1 (15.0 +/- 2.02 to 22.2 +/- 2.00 microU/ml, 1 h postcommencement of adenosine; P < 0.05 vs. saline). These data are consistent with observations in experimental animals and complement the results of previous studies in man using a selective adenosine A1-receptor antagonist, thereby confirming that adenosine has a significant regulatory influence on human renal function.