Sexually transmitted diseases (STDs) are highly prevalent in pregnant women in many developing countries and have been associated with poor obstetric outcomes. Case detection and treatment of STDs in women is problematic and expensive, underscoring the need for other strategies. To explore the potential benefits of routine antimicrobial therapy on pregnancy outcome, we carried out a randomized, double-blind, clinical trial in one of the antenatal clinics in Nairobi, Kenya. Four hundred pregnant women between 28 and 32 weeks' gestation were given a single dose of 250 mg ceftriaxone intramuscularly or a placebo. There was a significant difference between ceftriaxone and placebo-treated women in infant birth weight (3,209 versus 3,056 g, P = .01). In addition, there was a trend toward lower rates of birth weight < 2,500 g (4.0% versus 9.2%, P = .08) and postpartum endometritis (3.8% versus 10.4%, P = .05) in the intervention than in the placebo group. Neisseria gonorrhoeae was isolated from the cervixes of postpartum women in 1.8% of the intervention group as compared to 4.2% of the control group. These data suggest a beneficial effect of antimicrobial prophylaxis on pregnancy outcome. Larger studies should be carried out to examine the public health impact of this intervention.