To investigate the influence of antituberculous treatment on Cimetidin (Ci) disposition, 300 mg Ci were administered intravenously to 12 patients on triple drug therapy (Ethambutol 25 mg/kg/d, Isoniazid 8 mg/kg/d, Rifampicin (Rif) 8 mg/kg/d) and to 13 healthy subjects. Plasma levels and urinary recovery of Ci and its major metabolite Ci-Sulfoxide (CiS) were measured by HPLC. In patients on tuberculostatics nonrenal clearance (Clnr) increased by 52% (395 +/- 85 ml/min, controls 261 +/- 74 ml/min), while total clearance (ClB) (703 +/- 154 ml/min controls 632 +/- 118 ml/min) and volume of distribution (Vd beta) (1.35 +/- 0.33 l/kg, controls 1.6 +/- 0.37 l/kg) remained unchanged. The reduced renal clearance of Ci in the patients (308 +/- 125 ml/min, controls 371 +/- 115 ml/min) appeared to be mainly dependent on reduced renal function and not on antituberculous therapy. The CiS/Ci ratio in urine was unchanged in the patients (16 +/- 6.5, controls 20.5 +/- 10.6). The increased elimination of undegraded Ci via nonrenal pathways under tuberculostatic triple drug therapy may be a consequence of Rifampicin induced microsomal enzyme induction.