Abstract Serum levels of the soluble form of the CD 8 (s-CD 8) antigen were evaluated in the peripheral blood of 44 patients with B-CLL, using an enzyme-linked immunosorbent assay, and were correlated with clinical features and relevant hematological and immunological data. Increased values were observed with respect to normal age-matched controls (mean ± S.E.M. 603 U/ml ± 81 vs. 315 U/ml ± 31, respectively; P < 0.0001). This increase was observed in all stages of the disease, excluding stage 0 (mean 277 U/ml ± 45). A general trend pointing to lower values overall in patients with less invasive disease was observed. In fact, the rank correlation test showed that the serum levels of s-CD 8 correlate significantly with the WBC counts, the CD 4/CD 8 ratio, and also with the levels of serum immunoglobulins. On the contrary, no correlation was observed between s-CD 8 levels and the absolute number of circulating CD 8+ cells in individual cases. Therefore, the increase of s-CD 8 is unlikely to be a mere expression of the increase of the CD 8 cell number, but seems related to an increase of the activation phenomena involving the CD 8+ T cell subset.