To test the hypothesis that involuntary smoking can result in increased drug metabolism, five nonsmoking healthy male volunteers (21-36 y old) were enrolled in a study of single-dose theophylline pharmacokinetics before and after intense environmental tobacco smoke (ETS) exposure. Exposure was provided by spending 3 h/day for five consecutive days in a small room with a smoking apparatus that burned four cigarettes simultaneously, at a rate of 20 cigarettes/h. Measurement of urine continine concentration demonstrated that significant absorption from ETS occurred in all subjects. However, pre- and post-exposure pharmacokinetic parameters for theophylline did not differ significantly: Vz = 0.438 vs 0.440 l.kg-1; t1/2 = 9.19 vs 9.69 h; CL = 34.4 vs 32.6 (ml.kg-1.h-1), respectively. Similarly, 24-hr urinary excretion of theophylline and its metabolites was unchanged by ETS exposure. We conclude that intense short-term passive smoking does not affect theophylline disposition. The possibility of chronic ETS exposure causing alterations in drug metabolism cannot be excluded.