This paper presents clinical, immunological and post-mortem findings in three family members (husband, wife and daughter) who all died in 1976 after having had chronic and recurrent opportunistic infections for many years. In all of them a progressive, presumably acquired T-lymphocyte defect associated with B-lymphocyte dysfunction had been diagnosed several years before death. The clinical and immunological findings are compatible with those seen in acquired immunodeficiency syndrome (AIDS) caused by HTLV-III/LAV infection, but examinations of stored blood samples from the three patients were negative with regard to the presence of HTLV-III/LAV antibodies. This immunodeficiency may therefore have been caused by an infectious agent of unknown nature. The most remarkable finding on post-mortem examination was the presence of a granulomatous encephalomyelitis with multinucleated giant cells in the husband and his wife. In addition, the wife's CNS revealed scattered microglial nodules. No infectious agents could be demonstrated, and the etiology of this peculiar CNS affection therefore remains obscure.