An important element of the host response to cryptococcosis is humoral immunity. Specific antibody responses in patients with cryptococcosis however, have not been extensively studied. We analyzed the antibody responses of 22 Indian patients with cryptococcosis, including both HIV+ and HIV- individuals. Sera from 10 Indian patients with AIDS and without cryptococcosis were studied as controls. Antibody responses to cryptococcal proteins were detected by immunoblot, while antibodies to glucuronoxylomannan (GXM), the main component of the cryptococcal capsular polysaccharide were measured by ELISA. Our results indicate that cryptococcosis elicits antibodies to a specific pattern of cytoplasmic proteins. Further, we find that antibody responses to both cytoplasmic proteins and GXM are less robust in HIV+ patients when compared with HIV- patients.