Typhoid fever is an infectious disease with multisystem involvement and is commonly seen in the tropics. Twelve patients with acute typhoid fever were successfully treated with a fixed dose combination of pivmecillinam and pivampicillin. The treatment results were compared to those obtained from the treatment of ten other patients with co-trimoxazole, which is the routine treatment of our Department. The two forms of treatment appeared to be equally effective, suggesting that the combination mecillinam/ampicillin may represent a valuable alternative to the antityphoidal drugs currently available. Eleven patients were infected with strains resistant in vitro to either ampicillin, chloramphenicol, or both. All clinical isolates were sensitive to co-trimoxazole and to the combination of mecillinam and ampicillin. MIC values for the combination ranged from 0.16 to 2.5 mg/l. No side-effects were recorded.