Kinetics of metronidazole and its metabolites were examined after single oral and intravenous doses and multiple oral doses in seven subjects by a sensitive HPLC assay. After 400 mg metronidazole IV, mean Vd beta was 1.05 l/kg. Mean plasma t1/2 was 8.3 hr with a ClTBC of 1.31 ml/min/kg. Clearance to the major metabolites, 2-hydroxy-metronidazole and 1-acetic acid metronidazole, accounted for over 90% of the ClTBC. After a single oral 400-mg metronidazole dose, the development of peak metronidazole plasma concentrations of 6.9 micrograms/ml averaged 2.3 hr after dosing. Systemic oral bioavailability was complete (98.9%). During twice-daily multiple metronidazole dosing, 400 mg, metronidazole kinetics were the same. Elimination t1/2 was 8.3 hr and average predicted steady-state metronidazole concentrations during one dosing interval (6.3 +/- 0.5 micrograms/ml; mean +/- SE) were equal to the observed concentrations (6.9 +/- 1 micrograms/ml). Urinary excretion of unchanged metronidazole was below 10% of the total dose. Seventy-five percent of the dose was 2-hydroxy-metronidazole and 1-acetic acid metronidazole, and 15% was conjugates of metronidazole and 2-hydroxy-metronidazole.