SUMMARY The blastic transformation in vitro of peripheral blood lymphocytes was measured by the 72-hour uptake of tritiated thymidine (3H-6-thymidine) in 23 patients with mucosal ulcerative colitis, three patients with acute Crohn's colitis with rectal involvement, and seven normal subjects. The 23 patients with ulcerative colitis were subdivided into three groups, graded according to severity into seven with acute, severe, nine with active, chronic, and seven with quiescent disease.In the control cultures of lymphocytes without any added potential stimulant the uptake of 3H-6-thymidine in the clinical subgroup of seven patients with acute, severe ulcerative colitis was significantly greater than in seven normal subjects (P <001). This contrasted with a reduced uptake of 3H-6-thymidine by lymphocytes from seven patients with acute severe colitis when compared with seven normal subjects after stimulation with phytohaemagglutinin-P (PHA-P) (P < 0.01).In further duplicate cultures of lymphocytes specifically stimulated by an equal number of viable autologous rectal epithelial cells, the uptake of 3H-6-thymidine was significantly greater in seven patients with acute severe colitis when compared with seven normal subjects (P < 0.01). The results in three patients with acute Crohn's colitis with rectal involvement showed no such evidence of lymphocyte sensitivity to autologous rectal epithelial cells and their uptake of 3H-6-thymidine lay within the normal range.Evidence that the degree of lymphoblastic transformation was related to the clinical severity of ulcerative colitis was provided by the results obtained in the unstimulated and epithelial cell stimulant cultures. The uptake of 3H-6-thymidine was directly related to the clinical severity of ulcerative colitis in the three subgroups studied.In addition, four of the seven patients with acute severe colitis were studied later in clinical remission. They were then found to have a significantly reduced uptake of 3H-6-thymidine in response to autologous rectal epithelial cells (P < 0.01).In the normal cellular immune response blastic transformation of thymically directed lymphocytes is an important component of the process of recognition of certain antigens by the host. This transformation leads to the production of a group of effector cells which mediate a specific response against that antigen (Roitt, Greaves, Torrigiani, Brostoff, and Playfair, 1969). Lymphocytes from patients with ulcerative colitis have been found to damage autologous colon epithelial cells in culture