A double-blind placebo-controlled experiment was performed in 100 patients in labor with membrane rupture to determine the bacteriologic effects of antibiotic prophylaxis. Each subject received either 2.0 g cefamandole or placebo after cord clamping and 4 and 8 hours later. The cefamandole group had significantly less endometritis, but did not have significantly fewer major complications. Amniotic fluid cultures of the 2 groups were similar, but uterine lavage cultures of the cefamandole group showed significant increases in enterococci and gram-negative aerobes and decreases in gram-positive anerobes and low virulence organisms (Staphylococcus epidermidis, lactobacilli, and diphtheroids). Although clinical problems did not regularly accompany these changes, it would be foolhardy to ignore them. Thus, when patients develop infection after antibiotic prophylaxis, the physician should check for infection with resistant organisms.