Immunoglobulin levels and antibody activities have been studied in patients with either acute or chronic histoplasmosis in order to define more completely the humoral immunological response in this disease. The sequential immunoglobulin response in acute histoplasmosis is typical, with an early IgM rise followed by an increase in IgA and IgG levels. Patients with the chronic form of the disease have markedly elevated IgA levels (mean 431 mg/100 ml) and relatively normal IgM and IgG levels. Latex-agglutinating antibody activity appears to reside in the IgM fraction, while precipitating antibody activity is located in the IgG fraction. Complement-fixing activity was found primarily in IgG and, less often, in IgM.