To obtain prevalence data on Cryptosporidium infection in healthy US adults and to determine how often Cryptosporidium infection occurs after relocation to a situation of potentially great exposure, an enzyme-linked immunosorbent assay for anti-Cryptosporidium IgM or IgG was used to examine serum from 75 US Peace Corps volunteers before overseas service and after up to two years in West Africa. Of the volunteers, 32% had detectable anti-Cryptosporidium IgG initially, suggesting that infection sometime in life is common. After six weeks, one year, or two years overseas, 5% (1/19), 14% (8/56), and 13.6% (3/22), respectively, became newly IgG positive. This implies that the risk of acquiring Cryptosporidium infection and its associated diarrhea is real for travelers and temporary workers in endemic areas. Persistence of IgG and/or IgM response for 12 months or more occurred in some volunteers, although the significance is unclear.