The protective efficacy of oral bovine immunoglobulin concentrates derived from colostrum against challenge with Shigella flexneri was studied in healthy adult volunteers in a randomized, double-blind fashion. Volunteers were given a product consisting of hyperimmune immunoglobulin concentrate with a high titer of anti-S. flexneri 2a lipopolysaccharide (LPS) with sodium bicarbonate or a control preparation with sodium bicarbonate three times a day for seven days. On the third day of treatment, volunteers received a challenge of 103 colony-forming units of S. flexneri 2a strain 2457T. None of the volunteers who received the high-titered hyperimmune product became ill, compared with 45% of volunteers who received the placebo (P < 0.05). The duration of shedding of the challenge organism was decreased, and the active immune responses to S. flexneri LPS were less frequent and of lower magnitude in volunteers given the immunoglobulin concentrate than in those in the control group. High-titered, orally administered bovine immunoglobulin concentrate protects against shigellosis and may be useful in preventing shigellosis among travelers, military personnel, and individuals at risk during a Shigella outbreak.