Antibodies reactive with the cryptococcal polysaccharide glucuronoxylomannan (GXM) are present in sera from both human immunodeficiency virus (HIV)-uninfected and -infected adults. However, the prevalence of these antibodies in US children is unknown. An antigen-capture ELISA was used to determine the presence, serotype specificity, isotype, and IgG subclass distribution of antibodies to GXM in sera from 27 HIV-uninfected and 34 HIV-infected children. The children were of similar age and socioeconomic background. IgG and IgM to GXM were present in sera from all children, although HIV-uninfected children had significantly higher titers. HIV-uninfected children had IgG1 and IgG2 to GXM and significantly greater IgG2 than in HIV-infected children. These findings of type-specific antibodies to GXM in early childhood suggest that exposure to or subclinical infection with Cryptococcus neoformans may be an early childhood event.