The pathogenic potential of Blastocystis hominis in the human intestine is subject to controversy because the organism has been found in both symptomatic and asymptomatic individuals. To help clarify this issue, we monitored the serologic response to the organism in B. hominis-infected individuals free of gastroenterologic disorders. 1) Serum antibodies to B. hominis were detected in 70% of infected asymptomatic individuals by an indirect immunofluorescence (IFA) test. 2) IFA and immunoelectron microscopy revealed that the antibody response was directed against a surface antigen(s) of the organism. 3) Analysis by immunoblotting implicated a 12 kDa protein of B. hominis. 4) The strongest positive reaction was obtained in an individual chronically infected for more than 2 years. It may be that long exposure to the parasite is necessary for a serologic response.