Since 1989, 21 persons with unexplained CD4+ T-lymphocyte depletion, but without evident human immunodeficiency virus (HIV) infection, have been described (1-12). These reports included persons who have resided in the United States and six other countries and who sought medical care for conditions often associated with immune deficiency. Some of these cases were also described at the VII International Conference on AIDS/III STD World Congress in Amsterdam. In addition, CDC has received reports of five persons from three states who have had persistently low CD4+ T-cell levels but who have had no evidence of HIV infection or underlying disease processes or therapies known to be associated with T-cell depletion. In some of these five patients, opportunistic infections were diagnosed that frequently occur in persons with acquired immunodeficiency syndrome (AIDS). This report describes preliminary clinical and laboratory findings from an ongoing investigation by CDC of these five patients.