For the period 1976-1985, the authors attempted to identify all cases of blastomycosis in Louisiana and studied in detail one county (Washington Parish) suspected by local physicians of having an unusually high incidence of the disease. The mean annual incidence rates for Louisiana and for Washington Parish were 0.23 and 6.8 cases per 100,000 population, respectively. To the authors' knowledge, the rate for Washington Parish is the highest annual incidence rate documented for a population in a nonoutbreak setting. Among the 30 cases detected in Washington Parish, the age range was 3 weeks to 81 years. Five cases died; of these, one was an infant who may have been infected in utero, and another developed clinical symptoms compatible with adult respiratory distress syndrome. There was no geographic clustering among cases the authors investigated, and a case-control study failed to identify specific activities or host factors which may have predispose to infection. Washington Parish is probably a hyperendemic area for blastomycosis because environmental conditions are especially conducive to Blastomyces dermatitidis growth. The study suggests that most cases in Washington Parish were sporadically infected, and common-source exposures to B. dermatitidis with resultant clinical illness are rare even in hyperendemic settings.