To establish elimination kinetics of mezlocillin in patients with hepatic insufficiency, we gave eight normal subjects and four patients with hepatic insufficiency and normal renal function a single 3-gm dose of mezlocillin by intravenous infusion. Subjects with hepatic insufficiency all had serum bilirubins levels of above 3 mg/dl, prothrombin times more than 2 sec longer than control, and creatinine clearances above 60 ml/min. Mezlocillin concentrations were determined by microbiologic assay. Kinetic analysis was by model-independent methods. Elimination half-life was 0.96 hr for subjects with normal liver function and 2.62 hr for patients with hepatic insufficiency. Mean total body clearance for normal subjects was 247 ml/min, while in patients with hepatic insufficiency it was 125.4 ml/min. We conclude that hepatic insufficiency prolongs mezlocillin elimination and suggest that therapeutic guidelines be set up.