In order to clarify the epidemiology and clinical spectrum of endemic blastomycosis, we reviewed the charts of 326 culture and/or histologically proven cases of blastomycosis in Mississippi from 1979 to 1988. Cases were dispersed throughout the state, but counties in central and south-central Mississippi reported 63% of all blastomycosis cases. The average annual incidence rate was 1.3 cases per 100,000 population. The majority of cases were in men (male to female ratio 1.7:1), and most patients were aged in their third through seventh decades (82%). Outdoor occupations were noted for only 28.9% of cases. Cases occurred throughout the year with no significant seasonal peak. Although 55% saw a physician within 7 days of onset of illness, 29% presented after 1 month. Despite early presentation, diagnosis was often delayed for more than 1 month (43.3%). Single organs were involved in 82.8% of cases. For all cases, organ systems involved included lungs (91.4%), skin (18.1%), bone (4.3%), genitourinary system (1.8%), and central nervous system (1.2%). The presence of skin or bone disease was associated with multiorgan involvement. Thirty-three patients died (11.5%), 6 of whom received no therapy. Patients who died were significantly older than those who survived. A successful outcome without relapse was noted in 86.5% of amphotericin B-treated patients and in 81.7% of ketoconazole-treated patients. The relapse rate for ketoconazole-treated patients was higher than for amphotericin B-treated patients (14% and 3.9% respectively).