To evaluate the safety of vitamin A supplementation in early infancy using DPT/OPV immunization contracts, a double-blind, randomized, placebo-controlled trial was conducted in Bangladesh. One hundred and sixty-seven infants received three doses of either 25,000 IU of vitamin A or a placebo at about 6.5, 11.8 and 17.0 weeks of age. Trained physicians examined each of the infants on days 1, 2, 3 and 8 after supplementation. Nine infants (10.5%) supplemented with vitamin A had episodes of bulging of the fontanelle compared with two infants (2.5%) in the placebo group (p < 0.05). Twelve of the 14 episodes occurred in infants supplemented with vitamin A. Of these 12 episodes, none occurred with the first dose, 3 occurred with the second and 9 with the third dose. The higher incidence of bulging of the fontanelle in the vitamin A group relative to the placebo group and its temporal association with the vitamin A doses are suggestive of a causal association. The finding that increased numbers of vitamin A doses were associated with a higher probability of bulging of the fontanelle suggests a cumulative effect.