The frequencies of erythrocyte MNSs antigens and certain histocompatibility leukocyte antigen (HLA) specificities (HLA-A, HLA-B, and HLA-DR) were determined in white patients with meningitis or epiglottitis due to Haemophilus influenzae type b and in controls. The frequency of the erythrocyte MNSs genotype was significantly lower among patients with meningitis than among those with epiglottitis (P = 0.03); this observation confirms a trend observed previously. However, the frequencies of the HLA specificities did not differ significantly in the three groups studied; this result fails to confirm previous reports of disease associations with several HLA-A and HLA-B specificities. Although susceptibility to different clinical manifestations of haemophilus disease may be influenced by genetic factors, our studies indicate that the major loci conferring susceptibility are not in linkage disequilibrium with specificities in the major histocompatibility complex.