Opportunistic infections are common and major causes of morbidity in patients with AIDS. Endemic mycoses pose serious risks for patients in certain parts of the world. Histoplasmosis occurs in 2-5% of patients with AIDS in the Ohio and Mississippi River valleys of the United States and in over 25% of patients from a few cities. Antigen testing has become a highly useful method for diagnosing histoplasmosis rapidly, evaluating the response to treatment and diagnosing relapse. Treatment with amphotericin B or itraconazole is effective (90% or higher) if the patient is not seriously ill at the time of diagnosis but the mortality approaches 50% for those with multiorgan failure. Itraconazole blood levels should be monitored and drugs that impair the absorption or accelerate the metabolism of itraconazole should be avoided. Prophylaxis with itraconazole may be appropriate in areas with an incidence of histoplasmosis. A recently completed study in cities which have unusually high rates of histoplasmosis will provide greater insight into the role of prophylactic antifungal therapy.