The in vitro antimicrobial activity of two newer agents, ticarcillin and cefoxitin, against 204 recent clinical isolates of anaerobic bacteria was determined by an agar dilution technique, and compared to their related compounds carbenicillin, cephalothin, and penicillin, as well as metronidazole, clindamycin, and chloramphenicol. Ticarcillin was similar to carbenicillin, and cefoxitin was more active than cephalothin. At readily achievable blood concentrations of each antimicrobial agent, ticarcillin was slightly less active than clindamycin against Bacteroides fragilis. Cefoxitin was superior to cephalothin and penicillin against B. fragilis. Penicillin remained highly active against all obligate anaerobes other than B. fragilis. Metronidazole, while highly effective against B. fragilis and Clostridium perfringens, was only intermediately effective against anaerobic gram-positive cocci and relatively inactive against nonsporulating anaerobic gram-positive bacilli. Further evaluation of the clinical efficacy of ticarcillin, carbenicillin, and cefoxitin against anaerobic infections is indicated.