The renin-angiotensin system plays an important physiological role and has prognostic significance in cirrhotics with ascites. The degree of stimulation of this system is usually estimated by measuring plasma renin activity after incubation periods of 2-3 h. Recent investigations showed that the direct measurement of immunoreactive renin also estimates the degree of activity of the system. In this study, immunoreactive renin and plasma renin activity (measured at incubation periods of 10, 20, 50 and 180 min) were determined in ten healthy subjects, five hyperreninemic non-hepatic patients and 47 cirrhotics with ascites. Cirrhotic patients showed significantly higher plasma renin activity (5.1 +/- 0.9 ng/ml per h, p < 0.05) and immunoreactive renin (145.4 +/- 24.4 pg/ml, p < 0.01) than healthy subjects (1.2 +/- 0.15 ng/ml per h and 25.1 +/- 1.1 pg/ml, respectively). The angiotensin I generation rate was constant during the 3-h incubation in 22 cirrhotics and a close relationship (r = 0. 956, p < 0.001) between plasma renin activity (3.5 +/- 1.6 ng/ml per h) and immunoreactive renin (71 +/-25 pg/ml) was observed in these patients. In the remaining 25 cirrhotics the generation rate of angiotensin I declined with time and the calculated plasma renin activity at 180 min was lower than the activity calculated at 10 min by 50.7%. In this group the slope of the regression line (0.019 +/- 0.004) between immunoreactive renin (210 +/- 35 pg/ml) and the 180 min plasma renin activity (7.1 +/- 0.9 ng/ml per h) was significantly different (p < 0.001) than the slope obtained with 10 min plasma renin activity (13.6 +/- 1.8 ng/ml per h; slope: 0.043 +/- 0.005). These results indicate that plasma renin activity, measured after 3-h incubation, underestimates the degree of stimulation of the renin-angiotensin system in a high percentage of cirrhotics with ascites and that immunoreactive renin measurement improves the assessment of the system in these patients.