The pharmacokinetics of bupropion hydrochloride, a structurally novel antidepressant agent, have been studied in healthy male and female subjects following administration of single oral doses of 50, 100 and 200 mg. Plasma drug concentrations were determined directly by a specific radioimmunoassay (r.i.a.), while urinary measurements required a prior solvent extraction to remove substances interfering in the assay. Bupropion appeared rapidly in the plasma, suggesting good absorption. Drug plasma concentration-time data were fitted well to a two-compartment open model of drug disposition by use of the computer program NONLIN. By comparison of AUC, Cmax and tmax values, the pharmacokinetics of bupropion were found to be linear across the 50-200 mg dose range in both sexes. When the data were normalized for subjects' body weights, no differences between pharmacokinetic parameters for male and female subjects were found. Mean disposition half-lives across treatments were 1.2-1.4 h for t1/2 alpha and 10.7-13.8 h for the t1/2 beta. Bupropion was extensively bound (85%) to human plasma proteins over a wide drug concentration range. Less than 1% of a 200 mg oral dose of bupropion hydrochloride appeared in the urine of 16 subjects as unchanged drug, indicating extensive metabolism of the parent compound.