Chronic pulmonary histoplasmosis is a disorder caused by Histoplasma capsulatum infection that is classically described as cavitary disease in male smokers with underlying chronic obstructive pulmonary disease (COPD). This clinical description relies on previous studies conducted mainly on cohorts from tuberculosis sanatoriums and United States Department of Veterans Affairs hospitals. Patients in earlier series were often selected either after being suspected of having Mycobacteria tuberculosis or by the presence of cavitary disease on chest radiograph. These early studies therefore may overrepresent the true proportion of males, smokers, and the percentage with cavitary disease in the general population. We sought to define the clinical spectrum of chronic pulmonary histoplasmosis in a mixed-sex inpatient and outpatient population. We conducted a retrospective chart review from 1976 to 2000 on all adults with a diagnosis of histoplasmosis with symptoms suggestive of pulmonary histoplasmosis for > or =6 weeks and either significantly positive serum H. capsulatum antibody titers or positive cultures (without evidence of disseminated disease). Participants included 46 patients, with a median age of 56 years. Notable differences were found between our study population and those in previously reported studies. First, nearly half of our patients were women (48%), and one-quarter were life-long nonsmokers (27%). Only 39% had cavitary disease and only 20% had COPD. It is noteworthy that there were no positive cultures from those patients who had never smoked. Major differences existed between male and female participants. Female patients had a lower presence of cavities, a decreased number of smokers and extent of smoking exposure, a decreased number of positive cultures, and an absence of underlying COPD. To our knowledge, this study is the first to report on a large number of outpatients with chronic pulmonary histoplasmosis. In contrast to previous studies, the current study included 48% female patients, 27% never smokers, and only 39% of patients with cavitary disease, representing a noticeably different spectrum of disease compared to previous studies.