Using monoclonal antibodies to the surface antigens or suppressor/cytotoxic (Anti-Leu-2a) and helper/inducer (Anti-Leu-3a) T cell subsets, we characterized peripheral lymphocytes in 27 patients with ulcerative colitis (UC) and 15 age-matched healthy controls by a fluorescence activated cell sorter. The patients with active UC had a reduced percentage (8.2 +/- 3.6%) of Anti-Leu-2a reactive subset in comparison with healthy controls (24.6 +/- 3.6%) (P less than 0.01). No significant change was found in the percentage of Anti-Leu-3a reactive T cells between the patients and the controls. Moreover, the relationship of lymphocytophilic antibodies found in the patients with UC to the T cell subsets was also examined. After a fraction of normal T cells was eliminated with treatment of the sera from patients with active UC, the percentage of T cells reactive with Anti-Leu-2a decreased from 25 to 15%, whereas the percentage of T cells reactive with Anti-Leu-3a increased from 40 to 70%. In the reciprocal study, the lymphocytophilic antibodies reacted with 80% of Leu-3a negative T cells and 65% of Leu-2a negative T cells. These results demonstrated that the lymphocytophilic antibodies found in UC patients are reactive with suppressor T cells and thus play an important role in the loss of peripheral suppressor cells in the active UC patients. The lymphocytophilic antibodies were also demonstrated to be reactive with non-helper, non-suppressor T cell subsets and some populations of helper T cells. These studies suggest the presence of immune-regulatory disturbances contributing the pathogenesis of UC.