Sulfamethoxazole (SMZ) plasma peak levels between 40 and 60 μg/ml of the total sulfonamide concentration, representing the unchanged drug and all its metabolites, and between 30 and 50 μg/ml of the potentially bacteriostatic fraction are reached within 2–4 h after ingestion of 800 mg SMZ alone or in combination with 160 mg trimethoprim (TMP). Plasma disappearance of SMZ is characterized by first order processes. Elimination half-lives average about 10 h for the total sulfonamide and about 8 h for the active fraction which represents almost exclusively the unchanged drug. Assuming total absorption the apparent volume of distribution for SMZ is approximately 11 liter. Steady-state plasma levels of 50–80 μg/ml of the total SMZ and of 32–47 μg/ml of the active fraction are achieved after 2–3 days and maintained on a chronic oral dosing schedule of 800 mg SMZ every 12 h. The average plateau concentration of the unchanged and bacteriostatically active drug is approximately 65% of the total sulfonamide concentration. Simultaneous application of TMP does not alter the pharmacokinetics of SMZ neither in case of single nor of chronic oral administration. Both drugs are, therefore, well suitable for combined clinical chemotherapy.