The in vitro activity of cefoperazone was tested against 155 clinical isolates of anaerobic bacteria and compared to that of cefoxitin, LY127935 (moxalactam), cefotaxime, cefamandole, and cephalothin. Against the Bacteroides fragilis group, the compound was as active as LY127935, but less active than cefoxitin. Cefotaxime was less active than cefoperazone, cefoxitin, and LY127935. Cefoperazone, as well as cefoxitin, LY127935, and cefotaxime, exhibited excellent activity against all other anaerobic organisms tested. Cefamandole and cephalothin showed inferior activity when compared to the other four drugs.