Attenuated Vibrio cholerae oral vaccineCVD 103-HgR was welltolerated by 324 Thai soldiers and civilians. Most receiveda single 5 X 10 8 cfu dose, while 40 each receivedone or two 5 X 10 9 cfu doses. Vibriocidal antibody (the best correlate of immunity) seroconversion was lower in soldiers than civilians (P < .001). Increasing the vaccinedose to 5 X 10 9 cfu raised the geometric mean titer (P < .001). A second 5 X 10 9 cfu dose one week later did not notably increase seroconversions. Likelihood of seroconversion was inverselycorrelated with baseline vibriocidal titer (P < .001). CVD 103-HgR caused seroconversion in most subjects with baseline titers .;;1:40, including 100% of civilians after one 5 X 10 8 cfu dose, 79% of soldiers after one 5 X 10 9 cfu dose, and 45% of soldiers after one 5 X 10 8 cfu dose. In persons with elevatedbaseline titers, vibriocidal antibody seroconversion is not a sensitive measure of whether vaccine has boosted intestinal immunity; for such subjects,other measurements must be used. Study regimens in endemic areas should use a single 5 X 10 9 cfu dose.Cholera remains an important public health problem in less-developed countries, spreading readily where sanitation is compromised and often appearing in explosive epidemics. The World Health Organization has targeted the development of an improved cholera vaccine as a priority [I, 2] because the parenteral inactivated whole cell vaccine, which provides only limited, short-lived protection, can play no practical role in cholera control [3]. An ideal new cholera vaccine would be well tolerated and rapidly stimulate a high level of long-term protection among all age groups after administration ofjust one oral dose. Such a vaccine would constitute a welcome addition to the public health intervention measures available to control epidemic and endemic cholera.An important advance in immunization against cholera was documented several years ago in a field trial in BanglaReceived 6 November 1991; revised 14 January 1992. The clinical protocol followed the guidelines of the Department of Health and Human Services and was reviewed by ethical committees at the University of Maryland at Baltimore. Mahidol University. and the US Department of the Army. The studies were explained in detail, and written informed consent was obtained.Grant desh when two related inactivated oral cholera vaccines (one consisting of inactivated Vibrio cholerae 0 I organisms and the other of inactivated organisms plus the B subunit ofcholera toxin) were each shown to confer 50% protection for 3 years [4]. That experience illustrates that oral vaccines can elicit relatively long-lived protection against cholera. However, the field trial in Bangladesh also exposed notable deficiencies of those oral inactivated vaccines: Multiple, spaced doses were required to elicit protection, young children (the population with the highest incidence ofcholera in that area) were least protected, and despite administration of three spaced doses, the level of efficacy was only 50%-52% [4].With a...