Fasting plasma caffeine concentrations, plasma levels of catecholamines and plasma renin activity were measured in patients with cirrhosis and control patients without hepatic dysfunction. A careful dietary history showed no significant difference in caffeine consumption (mean ± S.E.) among 46 cirrhotics (86 ± 7 mg per day) vs. 34 control patients (91 ± 8 mg per day). Fasting plasma caffeine concentrations, however, were significantly higher (7.68 ± 1.42 μg per ml) in cirrhotics than in controls (1.01 ± 0.20 μg per ml) (p < 0.01). Fasting plasma caffeine concentrations in cirrhotics varied significantly with Child's criteria, namely Child's A patients (2.06 ± 0.38 μg per ml); Child's B patients (6.92 ± 1.86 μg per ml), and Child's C patients (17.70 ± 3.65 μg per ml) (p < 0.001). In 44 cirrhotics, fasting plasma caffeine concentrations were compared with plasma levels of catecholamines and plasma renin activity. Plasma epinephrine concentrations were normal; however, plasma norepinephrine concentrations were increased in six cirrhotics, and plasma renin activities were increased in 28 cirrhotics. After a 3-day caffeine abstinence, plasma caffeine concentration and renin activity were significantly decreased (p < 0.01), and high plasma norepinephrine levels were also decreased in 12 cirrhotics. Plasma caffeine concentration, renin activity and norepinephrine level did not change in a control group of cirrhotics who continued to receive caffeine for 3 days (n = 6). After abstinence from caffeine, the decrease of fasting plasma caffeine concentration correlated well with the decrease of plasma renin activity (r = +0.746, p < 0.01). These results suggest that high levels of plasma renin activity and norepinephrine in cirrhosis are in part related to habitual intake of beverages with caffeine.