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 11) and 21 patients with benign structural or functional liver disease (Group 111). Group I patients had significantly lower systolic (113.0 f 2.2 mm Hg, mean f S.E.) and diastolic (65.3 f 1.7 mm Hg) pressures than Group I1 patients (125.8 f 3.5 and 76.6 2 1.5 m m Hg, respectively (p < 0.0001) or Group I11 patients (125.1 f 3.4 and 77.5 f 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 f 0.26 pM, mean f S.E.) than in Group I1 patients (0.41 f 0.05 pM) (p +: 0.005) or Group I11 patients (0.34 2 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 f 4.3 mm Hg decrease in systolic pressure (p < 0.05) and a 10.8 f 3.7 mm Hg decrease in diastolic pressure (p < 0.05). Control amino acids were not vasoactive. 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.