In this study we investigated the serological levels of the soluble form of the CD8 molecule (s-CD8) in 97 human immunodeficiency virus (HIV) seropositive patients. The control groups included 20 normal heterosexual subjects and 19 healthy seronegative subjects belonging to risk groups for AIDS. Our results show that patients with HIV infection have significantly higher levels of s-CD8 U/ml than the control groups. When the patients were further subdivided according to the Centers for Disease Control (CDC) classification, s-CD8 U/ml values were consistently increased in all HIV patients, irrespective of the CDC stages. No statistically significant correlation was found between the serological levels of s-CD8/ml and the absolute numbers of CD8 lymphocytes/mm3, in both HIV seropositive patients and control groups. Since in the more advanced stages of HIV infection (IV-A, IV-C1) the decrease in the absolute number of CD8+ cells was not followed by a decrease in s-CD8 levels, it is conceivable that an increased release and/or shedding of s-CD8 per cell might occur in these patients. In fact, when the results were expressed as s-CD8 units per CD8 positive cell (s-CD8/absolute number of CD8), the levels of s-CD8/cell were higher in patients belonging to the IV-A and IV-C1 CDC groups (1.94 U/cell +/- 0.33 and 3.39 U/cell +/- 0.5, respectively) compared to normal controls (P less than 0.001), HIV seronegative subjects at risk for AIDS (P less than 0.001), and the other patients' groups (II and III CDC groups, respectively, P less than 0.001 and P less than 0.001). The evidence herein provided that in patients with HIV infection s-CD8 levels are increased suggests a possible pathogenetic role of the cells involved in the release of this molecule.