We retrospectively identified 13 patients infected with human immunodeficiency virus (HIV) who had persistently positive coccidioidal serological tests without evidence of active coccidioidomycosis--to our knowledge, a heretofore undescribed phenomenon. The median duration of follow-up was 19 months. Five patients developed active coccidioidomycosis during this follow-up period; the median interval from the initial positive serological test to the development of active disease was 23 months. There were no significant differences between patients who developed active coccidioidomycosis and those who did not with regard to CD4 lymphocyte count or previous antifungal therapy. Moreover, when all 13 patients were compared with 21 patients who had HIV infection and active coccidioidomycosis, no differences were found with regard to age, race, risk factor for HIV infection, or initial CD4 lymphocyte count. In summary, persistently positive coccidioidal serological tests in HIV-infected patients appear to represent true coccidioidal infection and are associated with a significant risk of the development of active coccidioidomycosis.