In the study presented here immunologic markers and HIV RNA were related to specific antibody responses in 50 HIV-infected patients who had moderate immunodeficiency (median CD4+, 295) and were vaccinated with a pneumococcal polysaccharide vaccine. Low responses were associated with low IgG2 or high IgM levels ( P=0.01) and good responses with high IgG4 ( P=0.05) or IgG2 ( P=0.07) or low beta(2) microglobulin ( P=0.04) levels. A combination of IgG2 levels >1.0 g/l and IgM <1.6 g/l at baseline significantly predicted a twofold or better response in logistic regression analysis ( P=0.025). Neither CD4+ lymphocyte counts nor HIV RNA levels were predictive, but it should be noted that good antibody responses were not restricted to patients with high CD4+ cell counts or low HIV RNA levels.