Eighteen homosexual men who had had lymphadenopathy in two or more extrainguinal sites for more than 5 months but had no evidence of other illnesses or infections were studied. All had extreme malaise, and 90% had additional symptoms (fever, night sweats, weight loss or gastrointestinal dysfunction). They were compared with 10 healthy homosexual and 10 healthy heterosexual male controls. The mean numbers of circulating T8 (suppressor) lymphocytes were increased equally in the two homosexual groups, but the mean number of T4 (helper) lymphocytes was decreased only in the group with lymphadenopathy. The response to testing for recall anergy was diminished in both homosexual groups but was significantly lower in the group with lymphadenopathy. The serum immunoglobulin and complement concentrations and the numbers of circulating B lymphocytes were normal in each group. Seven of nine lymph node biopsy specimens showed characteristic hyperplasia and confluence of follicles. Thus, idiopathic persistent, generalized lymphadenopathy in homosexual men without opportunistic infections or malignant diseases appears to be a distinct syndrome; it may also be related to the acquired immune deficiency syndrome.