In this study we examine the sensitivity of Histoplasma capsulatum var capsulatum antigen detection for the diagnosis of histoplasmosis. This was a retrospective review of the sensitivity of antigen detection in patients who were diagnosed as having self-limited, chronic pulmonary, or disseminated histoplasmosis during an outbreak in Indianapolis, Ind. All patients had clinical and laboratory evidence of histoplasmosis, and specimens of urine or serum that were obtained from the patients were tested for H capsulatum var capsulatum antigen. Of the 195 patients who were studied, the following forms of the infection were found: disseminated (n = 108), self-limited (n = 70), chronic pulmonary (n = 14), and asymptomatic (n = 3). Antigen was detected in 92%, 21%, and 39% of the patients with the disseminated, chronic pulmonary, and self-limited forms of histoplasmosis, respectively. Tests for the antigen are most useful in patients with clinical findings of disseminated infection. Antigen detection also may be useful in those patients with more severe pulmonary involvement, especially during the first month of illness when serologic tests for antibodies may be negative.