We reviewed 18 cases of histoplasmosis in patients at risk for the acquired immunodeficiency syndrome seen at two New York City hospitals in the past 3 1/2 years. Seventeen patients were Hispanic, including 13 born in Puerto Rico and three in South America. Clinical presentation was subacute, with high fever, weight loss, and mild respiratory symptoms with well-maintained gas exchange. Five patients had normal chest roentgenograms. The most common chest roentgenographic abnormality was diffuse small nodules. A rapid diagnosis was established histologically in 72 percent of patients, most commonly by transbronchial lung biopsy; cultures were positive in 94 percent of patients while serology was positive in five of six patients. Mycobacterium tuberculosis was a concurrent, often unrecognized, pathogen in six cases. Most patients responded to amphotericin therapy. Histoplasmosis may represent an early sign of altered host immunity in the acquired immunodeficiency syndrome.