The pharmacokinetics of mezlocillin were examined after single 2- and 4-g intravenous injections to three groups of male patients with creatinine clearances of I >/= 60, II = 21 to 59, and III </= 20 ml min(-1) 1.73 m(-2). The decline in serum antibiotic levels was biphasic in all groups, and serum data were interpreted in terms of the pharmacokinetic two-compartment model. The mean elimination half-life of mezlocillin after the 2-g dose was 1.3, 1.5, and 2.3 h in groups I, II, and III, respectively. Equivalent values after the 4-g dose were 1.2, 1.6, and 4.4 h. In three functionally anephric patients the mean serum half-life of mezlocillin was 1.5 h during hemodialysis. Mean antibiotic levels in serum were greater than 10 mug ml(-1) for 4 h after the 2- and 4-g doses in group I and 8 h in group II. In group III, levels greater than 10 mug ml(-1) were maintained for 6 h after the 2-g dose and over 12 h after the 4-g dose. Mezlocillin distribution characteristics were largely independent of renal function and dose size. The only observable change occurred in the value of V(dss), which was significantly increased to 0.32 with 0.38 liter kg(-1) in severe renal impairment, compared to ca. 0.2 liter kg(-1) in subjects with normal or slightly impaired renal function. Cumulative 24-h urinary excretion accounted for 50, 40, and 3.2% of the dose in groups I, II, and III, respectively. Urine levels of mezlocillin were uniformly greater than the minimum inhibitory concentration for susceptible organisms for 12 h after dosing in all patients who produced urine. Because of the relatively small increase in the mezlocillin elimination half-life with declining renal function, dose reduction is necessary only in cases of severe renal impairment.