An enzyme-linked immunosorbent assay for the detection of rotavirus-specific immunoglobulin G (IgG), IgM, and IgA antibodies was used in a serological study of Traveler's diarrhea. The antigenically related simian rotavirus (SA-11) was used as antigen in this study. Serum was obtained from two groups of volunteers before travel (pre-travel) and at various times after arrival at their destination (post-travel). One group consisted of 47 American Peace Corps volunteers who traveled to Honduras, and the second group consisted of 66 Panamanian travelers who visited Mexico. An association between rotavirus and Traveler's diarrhea was found in each group with 36% of American Peace Corps volunteers and 30% of Panamanians with diarrhea demonstrating a greater than or equal to 4-fold increase in rotavirus antibody titers in the post- as compared to the pre-travel specimens. While no rotavirus-specific IgM antibody was detected in any serum tested, increases in specific antibody were found in both the IgG and IgA immunoglobulin classes.