The first live oral typhoid vaccine (strain Salmonella typhi Ty 21a) distributed under the trade name of "Vivotif" has been evaluated for safety and efficacy in volunteer studies and in large-scale, placebo-controlled, double-blind field trials. While the data demonstrated that the vaccine was well tolerated, the level of efficacy varied distinctly. It is probable that the differences observed can be chiefly attributed to the various vaccine formulations evaluated to facilitate the passage of the acid-sensitive vaccine strain through the acid environment of the stomach. Based upon these results, the initially marketed formulation (2 bicarbonate capsules + vaccine capsule) was changed to an acid-resistant capsule which was subsequently evaluated in a field trial conducted in Chile and involving 44,000 school age children. Following 4 years of surveillance, a protection rate of 70% was obtained. To further optimize the means of delivering the vaccine, a formulation consisting of lyophilized vaccine reconstituted in a buffer solution is now being evaluated in a Chilean and Indonesian field trial. A similar though less practicable formulation showed excellent efficacy (approximately 95%) in a previous Egyptian field trial.