Systolic and diastolic blood pressures were recorded in 176 ambulant patients with chronic liver disease, including 36 patients with compensated cirrhosis (Group I), 119 patients with noncirrhotic chronic liver disease (Group II) and 21 patients with benign structural or functional liver disease (Group III). Group I patients had significantly lower systolic (113.0 ± 2.2 mm Hg, mean ± S.E.) and diastolic (65.3 ± 1.7 mm Hg) pressures than Group II patients (125.8 ± 3.5 and 76.6 ± 1.5 mm Hg, respectively (p < 0.0001) or Group III patients (125.1 ± 3.4 and 77.5 ± 2.4 mm Hg, respectively) (p < 0.0001). Serum levels of GABA, a potent amino acid neurotransmitter with known vasodilatory effects in vitro, were higher in Group I patients (1.12 ± 0.26 μM, mean ± S.E.) than in Group II patients (0.41 ± 0.05 μM) (p < 0.005) or Group III patients (0.34 ± 0.03 mM) (p < 0.05). A constant infusion of GABA into the systemic circulation of six adult dogs, at rates required to achieve serum GABA levels within one order of magnitude of those observed in humans with cirrhosis, resulted in a 17.0 ± 4.3 mm Hg decrease in systolic pressure (p < 0.05) and a 10.8 ± 3.7 mm Hg decrease in diastolic pressure (p < 0.05). Control amino acids were not vas-oactive. The results of this study suggest that, in addition to other vasoactive compounds, a GABA-mediated process might contribute to the hypotension observed in patients with compensated cirrhosis.