In 1996, serological responses to two Cryptosporidium antigens were determined for 200 Las Vegas (LV), Nevada, and 200 Albuquerque, New Mexico, blood donors to evaluate associations between endemic infections, water exposures, and other risk factors. LV uses chlorinated filtered drinking water from Lake Mead while Albuquerque uses chlorinated ground water. The intensity of serological response to both markers was higher for older donors (P < 0·05), donors who washed food with bottled water (P < 0·05) and donors from LV (P < 0·05). A decreased serological response was not associated with bottled water consumption, nor was an increased response associated with self-reported cryptosporidiosis-like illness or residence in LV at the time of a cryptosporidiosis outbreak 2 years earlier. Although these findings suggest the serological response may be associated with type of tap water and certain foods, additional research is needed to clarify the role of both food and drinking water in endemic Cryptosporidium infection.