Serum levels of IgA, IgM, and polyvalent immunoglobulins reactive with Clostridium difficile were determined by ELISA for asymptomatic carriers (n = 5), symptomatic individuals (n = 21), and a pool of 30 "normal" individuals. Mean IgA concentrations expressed as optical density (OD +/- SD) were significantly higher (P < .001) for asymptomatic carriers (1.252 +/- 0.516) than for symptomatic patients (0.374 +/- 0.145). Mean serum IgM levels also were significantly higher (P < .001) for carriers (1.456 +/- 0.582) than for symptomatic patients (0.727 +/- 0.331), as were mean values for polyvalent immunoglobulins (2.25 +/- 0.718 for carriers vs. 1.457 +/- 0.574 for symptomatic patients; P < .05). Although the patient populations were small, the levels of immunoglobulins reactive with C. difficile antigens differed significantly. This difference might reflect the ability of the host to mount an immune response and might be a factor influencing whether a patient develops disease due to this organism. The ability to detect differences in immunoglobulin levels might also help differentiate infection from colonization.