Seven antibiotics, administered in 10 different regimens for prophylaxis, were randomly assigned to 1580 patients who were delivered by cesarean section. Cefazolin 1 gm, administered for three doses, served as the control group. Cefazolin 1 gm, cefazolin 2 gm, cefoxitin 1 gm, cefoxitin 2 gm, cefonicid 1 gm, cefotetan 1 gm, ceftizoxime 1 gm, ampicillin 2 gm, and piperacillin 4 gm were all administered in a single dose. Four antibiotics proved to be superior in preventing postpartum endometritis: ampicillin 2 gm (p = 0.03), cefazolin 2 gm (p = 0.005), piperacillin 4 gm (p = 0.0007), and cefotetan 1 gm (p = 0.0001). Single-dose cephalosporin antibiotic prophylaxis was found to result in approximately a twofold increase in Enterococcus faecalis colonization of the vagina (p less than 0.01). This may be significant in patients in whom postpartum endometritis develops and who have failure of initial treatment with a broad-spectrum cephalosporin, e.g., cefoxitin or cefotetan, or a combination such as clindamycin or metronidazole plus an aminoglycoside. Rupture of amniotic membranes for a half hour or more was associated with an increased risk for postpartum endometritis. The use of internal fetal monitoring was associated with an increased risk of soft tissue pelvic infection.