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Enterotoxigenic Escherichia coli (ETEC), which produces heat-labile toxin (LT), is a common cause of travelers' diarrhea (TD). The B subunit of ETEC LT is immunologically related to the B subunit of Vibrio cholerae toxin (CT). In this pilot study we evaluated the whole-blood gamma interferon response to CT B in 17 U.S. adults traveling to Mexico. Only one of nine subjects who demonstrated a cellular immune response as determined by whole-blood gamma interferon production to CT B on arrival to Mexico developed diarrhea, whereas five of eight without a cellular response developed diarrhea. Markers of the cellular immune response to ETEC LT could help in identifying individuals immune to ETEC LT, and these markers deserve additional study.Enterotoxigenic Escherichia coli (ETEC) is the most common cause of travelers' diarrhea (TD) in U.S. visitors to Mexico (1). ETEC isolates can produce heat-labile toxin (LT), heat-stable toxin (ST), or both toxins simultaneously (8). The LT of ETEC is highly homologous to the Vibrio cholerae toxin (CT) (4) and is composed of five beta-subunits that bind to the intestinal epithelial cell and a single alpha-unit that activates intracellular adenyl cyclase by virtue of its ADP-ribosylating activity. In addition to being an enterotoxin, LT is a potent mucosal adjuvant (5).In travelers, natural exposure to the ETEC LT is associated with a humoral immune response to LT; however, serum LT antibody titers resulting from naturally acquired ETEC LT do not correlate with long-lasting protection (11,12). This suggests that other components of the immune system are important in developing protective immunity to ETEC LT.Little is known about the protective effect that cellular immunity provides against ETEC LT and V. cholerae. In mice, immunization with the B subunit of the ETEC LT induces early CD4ϩ Th1-type and late CD4 ϩ Th2-type activation in Peyer's patches (10). In humans, individuals suffering from acute cholera show increased CD4 ϩ and CD8 ϩ T-cell proliferative responses against V. cholerae during the acute and convalescent stages of infection. Gut-homing CD4 ϩ T cells (␤7 ϩ ), gut-homing CD8 ϩ T cells (␤7 ϩ ), and gut-homing B cells (CD19 ϩ ␤7 ϩ ) also increase during the late convalescent stage of cholera compared to the acute stage of disease (2). This suggests that cellular immunity is important in the response to V. cholerae infection.We conducted a pilot prospective study to evaluate the cellular immune response to ETEC LT as evidenced by the whole-blood gamma interferon response to the B subunit of CT in U.S. adults traveling to a region where ETEC is endemic. Seventeen white non-Hispanic U.S. adults traveling to Cuernavaca, Mexico, for 3 weeks during July and August 2007 were enrolled in the study. Thirteen were women (76.5%), and the mean age at arrival was 28.6 years (standard deviation [SD], 11.6). TD was defined as the passage of three or more unformed stools within a 24-hour period plus one or more abdominal symptom of enteric infection. Six (35.3%) partici-