Two inclusions of the endoplasmic reticulum, tubuloreticular inclusion (TRI) and cylindrical confronting cisternae (CCC), are common to lymphocytes from individuals with AIDS and AIDS-related conditions. Both inclusions can be induced in vitro with alpha-interferon (IFN). IFN may also be elevated in both populations. Circulating lymphocytes containing TRI are seen prior to the appearance of serum IFN. CCC appear in circulating lymphocytes after TRI, and both regularly antedate the diagnosis of AIDS. As in systemic lupus erythematosus (SLE), it can be hypothesized that lymphocytes exposed locally to IFN acquire TRI and then appear in the peripheral blood to be followed subsequently by IFN. The data strongly suggest that the appearance of these markers may predict the progression to AIDS.