Soluble CD54 levels in sera were quantitated in asymptomatic intravenous drug users, homosexuals, and patients with lymphadenopathy, AIDS-related complex, or acquired immunodeficiency syndrome. Soluble CD54 levels were elevated in human immunodeficiency virus (HIV)-seronegative asymptomatic intravenous drug users, reflecting infections like cytomegalovirus, Epstein-Barr virus, and hepatitis B virus. The sera of human immunodeficiency virus-seropositive groups of patients also had elevated levels of soluble CD54, reflecting infections like cytomegalovirus and human immunodeficiency virus infection.