Between 1992 and 1999, 93 cases of blastomycosis, including 25 laboratory confirmed cases, were identified in Missouri (annual incidence, 0.2/100,000 population). Mississippi County in southeastern Missouri had the highest incidence (12/100,000) with a much higher rate among blacks than whites in this county (43.21/100,000). The mortality rate, 44% was also higher among blacks. To determine risk factors for endemic blastomycosis, a case-control study was conducted among southeastern Missouri residents. Independent risk factors for blastomycosis were black race and a prior history of pneumonia. No environmental exposures or socioeconomic factors were significantly associated with increased risk. The increased risk among blacks may possibly be related to genetic factors, but further studies are needed to clarify this. However, heightened awareness of the disease and a better understanding of the risk factors are important and may lead to earlier diagnosis and start of treatment, possibly improving outcome.