High levels of serum beta 2-microglobulin have been associated with human immunodeficiency virus infection and beta 2-microglobulin has been used with other serological and immunological markers for monitoring disease progression. The usefulness of beta 2-microglobulin as a prognostic marker during human immunodeficiency virus infection has been demonstrated in homosexual men and hemophiliacs; few and contradictory data have been reported in intravenous drug users. We have evaluated a cohort of 160 intravenous drug users (81 seronegative and 79 seropositive for human immunodeficiency virus infection) with normal renal function to assess whether serum beta 2-microglobulin could be used as a serological marker for monitoring infection; 78 healthy subjects were used as controls. Of 79 seropositive drug users, 54 were asymptomatic or had persistent generalized lymphoadenopathy the remaining 25 had the acquired immunodeficiency syndrome. Seropositive patients were tested for CD4+ lymphocyte number, p24 antigen and anti-p24 antibodies. A significant statistical difference was found in mean serum beta 2-microglobulin levels between seronegative and seropositive drug users. Moreover, higher levels of beta 2-microglobulin were observed in acquired immunodeficiency syndrome patients compared with asymptomatic or patients with persistent lymphadenopathy. A significant relationship was also observed between increased concentration of beta 2-microglobulin and the serological and immunological markers which indicate human immunodeficiency virus disease progression.