CD8+ (suppressor/cytotoxic) T lymphocyte subpopulations were studied in the peripheral blood of patients with Crohn's disease by flow cytometry analysis. Consistent with earlier reports, increased numbers of CD8+CD57+ cells were observed as compared with controls. However, expanded CD8+CD57+ cells were not found to be present in a distinct clinical subset of patients. A substantial number of patients had enhanced numbers of DR+ and CD45RO CD8+ cells. In addition, high numbers of CD8+ cells which were CD57CD45RO double positive, and a correlation between numbers of CD8+CD57+ and CD8+DR+ lymphocytes were detected. By use of an enzyme immunoassay, significantly elevated levels of soluble CD8 antigen were demonstrated in patients' sera, and results were associated with ESR values. Taken together, the data suggest increased activation of CD8+ lymphocytes which might result from systemic disease activity. Disturbances within CD8+ lymphocytes do not seem to be specific to Crohn's disease since similar alterations could be observed in patients with another inflammatory condition, rheumatoid arthritis.