Plasma concentrations and urinary excretion of DTZ and its metabolites were determined in 20 healthy volunteers (10 males and 10 females) after they had each been given a single oral 90 mg dose of DTZ. DTZ and six of its metabolites which included N-monodesmethyl DTZ (MA), deacetyl DTZ (M1), deacetyl N-monodesmethyl DTZ (M2), deacetyl O-desmethyl DTZ (M4) and deacetyl DTZ N-oxide (M1NO) and deacetyl N,O-didesmethyl DTZ (M6), were determined by a sensitive and specific HPLC assay. The major metabolites measurable in the plasma of all the volunteers were MA, M1, and M2. The terminal half-lives (t1/2) of M1 and M2 were considerably longer than those of DTZ and MA. Less than 5% of the dose was excreted as unchanged DTZ in the urine over the 24 h period. The major urinary metabolite was MA, followed by M6, M2, and then M1. Except for the urinary excretion of M4 there were no statistically significant differences in any of the pharmacokinetic parameters between the males and the females. The mean 24 h urinary recovery of M4 was higher in the males than in the females (P < 0.05). However there were large inter-individual variations in the plasma concentrations and urinary excretion of DTZ and its metabolites with some parameters differing by more than 20-fold. In addition, O-desmethyl DTZ (Mx) and N,O-didesmethyl DTZ (MB) were identified as two other major urinary metabolites.