Twenty-four antimicrobial drugs were examined for rapidity of onset and magnitude of bactericidal activity against selected strains of Clostridium perfringens. Ceftriaxone, imipenem, metronidazole, mezlocillin, penicillin G, piperacillin, and teicoplanin reduced colony counts by at least 3 log10 units within 2-4 h after exposure. Clindamycin, fluoroquinolones, josamycin, and tetracycline caused delayed kill (greater than or equal to 99.9% reduction of viable counts at 4-22 h after exposure). Chloramphenicol and rifampin lacked bactericidal activity against 2 of 4 strains, whereas erythromycin, fusidic acid, and fosfomycin (with added glucose-6-phosphate) were merely inhibitory for all 4 strains. Imipenem and penicillin G were combined with 9 and 12 antimicrobial drugs, respectively. Essentially all drug combinations yielded indifferent effects; only penicillin G plus doxycycline resulted in an antagonistic effect against C. perfringens.