The spontaneous disappearance of the inhibitor to factor VIII (FVIII) was observed in two human immunodeficiency virus (HIV)-infected men with hemophilia A. Both men had end-stage HIV infection, one with acquired immune deficiency syndrome (AIDS) and one with severe AIDS-related complex (ARC). Loss of the inhibitor was associated with a fall in T4 helper lymphocytes to less than 100 per mm3 in both patients. Subsequent spontaneous and traumatic hemorrhages were treated successfully with standard doses of FVIII concentrate, resulting in adequate FVIII:C levels and good hemostasis. The mechanism by which the anti-FVIII inhibitor disappears is not known, but it is likely to be related to a quantitative decline in T4 cell number.