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The pharmacokinetics of zalcitabine (ddC) were studied in three groups of subjects with varying degrees of renal function: group I (n = 5), creatinine clearance (Clcr) 0-10 mL/min; group II (n = 10), Clcr 11-50 mL/min; and group III (n = 8), Clcr > 50 mL/min. Each patient received a single 0.75-mg oral dose of zalcitabine, and multiple blood and urine samples were collected over a 10-hour period after administration. Plasma and urine concentrations of zalcitabine were measured by high-performance liquid chromatography. No statistically significant differences were observed between the three groups in maximum concentration (Cmax), time to Cmax (tmax), or volume of distribution (V/F). Also, elimination half-life (t1/2), area under the concentration-time curve (AUC0-10), total body clearance (Cl/F), elimination rate constant (Ke), and renal clearance (Clr) did not differ significantly between the two groups with renal impairment (groups I and II). However, there was a significant difference in these parameters between groups with renal impairment (I and II) and group III. A linear correlation was observed between creatinine clearance (Clcr) and Clr, Ke, and Cl/F in all subjects. Clearance of zalcitabine is decreased after a single oral dose in patients with renal impairment. Dosage adjustment may be warranted in such patients, especially in those with severe renal impairment.