Abstract Increased activation of lymphocytes in inflammatory bowel disease is reflected by alterations of various immunological functions including enhanced spontaneous secretion of rheumatoid factor by mononuclear cells. Since in rheumatic diseases increased secretion of rheumatoid factor is associated with decreased levels of β-endorphin in circulating blood mononuclear leukocytes, we investigated levels of leukocyte β-endorphin in inflammatory bowel disease and compared them with those in hepatobiliary disorders and in healthy subjects. Levels of β-endorphin were measured in extracts from peripheral blood mononuclear leukocytes by radioimmunoassay. β-Endorphin levels ranged from 0 to 67 pg/10 6 cells. Mononuclear leukocytes from ulcerative colitis patients contained as much β-endorphin as those from healthy control subjects. In patients with Crohn′s disease, levels of β-endorphin were reduced by as much as roughly 50%. An inverse relationship was found between leukocyte β-endorphin on the one hand and erythrocyte sedimentation rate, blood granulocyte or thrombocyte counts, and C-reactive protein levels in plasma on the other. In patients with various hepatobiliary disorders including fatty liver disease, viral hepatitis, primary biliary cirrhosis, and cryptogenic or alcoholic cirrhosis, β-endorphin levels were not significantly different from the normal range values. Data indicate that leukocyte β-endorphin may be involved in regulation of the systemic inflammatory activity of Crohn′s disease.