Among the endemic mycoses, blastomycosis has been least often associated with disorders of immune function, but the data presented herein suggest that blastomycosis may occur more commonly in immunocompromised patients than was previously recognized. We have observed a marked increased in the number of immunocompromised patients with blastomycosis over the last 15 years, increasing from about 3% of patients seen between 1956 and 1977 to almost 24% patients seen between 1978 and 1991. The disease appears to be much more aggressive in immunocompromised than in normal hosts. Almost 30% of the patients in our series died secondary to blastomycosis, with most deaths occurring within 5 weeks following the diagnosis. Furthermore, almost one third of those patients who died of other causes had evidence of persistent blastomycosis at death. Multiple organ and central nervous system involvement were relatively common in this series. For these reasons, early and aggressive therapy with amphotericin B is indicated for most immunocompromised patients with blastomycosis. Oral therapy with an azole compound should probably be reserved for patients who have responded to a primary course of amphotericin B but who require additional or long-term suppressive therapy. Until more data are available, the newer azoles should be used with caution as primary therapy in immunocompromised patients with blastomycosis, and considered only in patients with limited disease and a stable underlying condition. Caring for the immunocompromised patient poses many diagnostic and therapeutic challenges to the clinician, and among those patients who have been exposed to areas endemic for blastomycosis, B. dermatitidis must be regarded as a potentially important opportunistic pathogen.