Twenty-four sera from healthy donors, 18 from HIV-positive patients (< 200 CD4+/mm3) and 18 sera collected before and during cryptococcosis from HIV-positive patients were analysed for the presence of humoral response to C. neoformans mannoproteins. Our results show that samples from healthy subjects and from HIV-positive patients had one of three antibody response profiles: (i) presence of reactive antibodies against both 105 and 80 kilodalton mannoproteins; (ii) presence of reactive antibodies against one of the two mannoproteins; or (iii) absence of reactive antibodies. Importantly the percentage of unreactive sera increased 6-fold in HIV-positive patients and more than 10-fold in patients with cryptococcosis. In addition, in the latter patients no variation of humoral response before and during cryptococcosis was observed. These results suggest that HIV-positive patients show a marked difficulty in mounting or maintaining antibody response to mannoprotein and this could contribute to predisposition to cryptococcosis.