Two HIV-seronegative patients with cryptococcal disease refractory to conventional antifungal therapy were submitted to an evaluation of the immune system. Hypogammaglobulinemia was found in both and associated with abnormal function of cell-mediated immunity. Hypogammaglobulinemia is considered as a possible predisposing factor for cryptococcal infection. The importance of the antibodies on the control of Cryptococcus neoformans infection is discussed.