Patients seropositive for human immunodeficiency virus (HIV) type 1 and seronegative control subjects were categorized by their haptoglobin phenotypes, which were determined by electrophoresis of hemoglobin-supplemented plasma samples followed by benzidine staining. The CD4 cell counts, determined by flow cytometry from peripheral blood mononuclear cells according to subject categories, were severely diminished in seropositive patients with the Hp2-2 phenotype (P<.025). In contrast, the CD4 cell counts for patients with the Hp0 phenotype remained relatively high (P<.025), compared with those of the controls. In seronegative patients, CD4 cell counts were generally high (P<.005), but they were more elevated in subjects with Hp2-2 and Hp1-1, although the differences were not significant. Thus, the Hp2-2 phenotype is associated with poor outcome in HIV-1 infection, whereas the Hp0 phenotype is associated with a better prognosis once the patient is infected with HIV-1. Haptoglobin polymorphism plays a significant role in HIV-1 infection and transmission.