Peripheral blood mononuclear cells from patients with either Crohn's disease or ulcerative colitis (collectively referred to as inflammatory bowel disease) are cytotoxic in vitro for isologous or allogeneic colonic epithelial cells. Utilizing the ability of thymus-derived (T) lymphocytes to bind sheep red blood cells to their surface and the property of bone marrow-derived (B) lymphocytes to display easily detectable surface immunoglobulin determinants, the cytoxicity of these lymphocyte subpopulations was tested. The results indicate that the mononuclear cell required for the lysis of colonic epithelium was not included within the bulk of T or B lymphocytes. Indeed, enrichment for cytotoxicity correlated best with enrichment for a mononuclear cell population lacking classical T or B markers. Additionally, mononuclear cells specifically adhering to plastic petri dishes coated with heat-aggregated immunoglobulin, and thus presumably bearing a surface Fc receptor, were enriched in their cytotoxicity. Alternatively, cells not adhering to aggregated Ig-coated petri dishes were relatively depleted of cytotoxicity. The implications of these findings as they relate to possible interactions between cellular and humoral immune mechanisms as a pathogenic mechanism for the colonic inflammatory process noted in patients with inflammatory bowel disease are discussed.