Enzyme-linked immunosorbent assay polyribosyl ribitol phosphate (PRP) antibody responses to Haemophilus influenzae type b conjugate vaccine (HbOC) given at 2, 4 and 6 months of age were retrospectively compared in 23 human immunodeficiency virus (HIV) and 24 non-HIV-infected infants, HIV-infected infants were divided into those who were P1 (asymptomatic) or P2 (symptomatic) by 1 year of age, The P2 group was further divided into P2A (mildly symptomatic) and >P2A (rapidly symptomatic) by 1 year of age. The post-third HbOC dose geometric mean antibody titer to PRP was significantly lower in 12 P2 infants (0.43 mu g/ml) than either the 11 P1 infants (5.03 mu g/ml, P < 0.05) or the 24 non-HIV infected infants (3.43 mu g/ml, P < 0.05), Within the P2 group, the geometric mean antibody titer to PRP was significantly higher in 5 P2A infants (1.63 mu g/ml) compared with 7 infants who were >P2A (0.17 mu g/ml, P < 0.05), After the third HbOC dose, PRP antibody titers were greater than or equal to 1.0 mu g/ml for 4 of 12 P2 compared with 9 of 11 P1 infants (P < 0.05). Within the P2 group, PRP antibody titers were >1.0 mu g/ml for 4 of 5 P2A compared to 0 of 7 infants who were >P2A (P < 0.05). HIV-infected infants with PRP antibody titers greater than or equal to 1.0 mu g/ml after the third HbOC dose had significantly higher mean CD4 counts (2842 cells/mm(3)) mm3) at the time of the third HbOC dose than those with lower PRP titers (1655 cells/mm(3)) (P < 0.05). We conclude that antibody responses to HbOC vaccine are poorest in rapidly symptomatic HIV-infected infants or those with low CD4 counts, Antibody responses exhibited by P2A and P1 infants were similar to those of non-HIV infected infants, The immunogenicity of an additional dose(s) of HbOC during infancy in those with advanced HIV disease needs to be investigated.