A newly formulated, oral, inactivated whole cell plus recombinant B subunit (WC/rBS) cholera vaccine was evaluated in US military personnel. In the first study, 74 subjects were given two doses 14 days apart. In the second study, 186 subjects were randomized into four groups; two groups received vaccine with either full (4 g) or half (2 g) strength bicarbonate buffer, and two groups received either full or half strength buffer without vaccine. Mild gastrointestinal symptoms were associated with full buffer (P =.02) but not with the vaccine. In the first study, 36% of all subjects and 55% with low prevaccination titers <1:40) had a ⩾2-fold rise in vibriocidal antibody level; >80% of subjects developed a 4-fold rise in anti-cholera toxin (CT) titers. Postvaccination IgA and IgG anti-CT titers were ∼1.5-fold higher among persons receiving full strength buffer (P =.05). The WC/rBS vaccine is safe and immunogenic in North Americans, although some mild gastrointestinal symptoms occur with the high concentration ofbuffer necessary to protect the B subunit from gastric acid denaturation. Prior immunity to cholera conferred by parenteral vaccine decreased vibriocidal antibody response.