Ninety patients infected with presumed penicillin resistant anaerobes were randomized to cefoxitin or clindamycin-aminoglycoside. Cefoxitin was comparable to clindamycin-aminoglycoside in cures of intestinal associated, 16 of 26 versus 11 of 21, and pelvic infections, 20 of 20 versus 22 of 23. Cefoxitin-resistant facultative-aerobic gram-negative rods were found in 16 of 45 patients with intestine associated infection. Probable antibiotic associated nephrotoxicity was less frequent in the patients in the cefoxitin group, zero of 46 versus seven of 44, p less than 0.05, although a false creatinine elevation was noted more frequent, seven of 46 versus one of 44, p less than 0.05. Infections causing failure in patients in the cefoxitin group more frequently contained cefoxitin resistant gram-negative rods at the time of failure than did infections causing failure in those in the clindamycin-aminoglycoside group that contained gentamicin-resistant gram-negative rods, eight of eight versus zero of eight, p less than 0.001. Cefoxitin may be adequate therapy for many patients with mixed anaerobic/aerobic infections; however, the addition of an aminoglycoside may be prudent in those with known, or suspected, cefoxitin resistant gram-negative rods.