Monokines, in particular the interleukin-1 family and tumour necrosis factor alpha, have been implicated in the pathogenesis of chronic inflammatory bowel disease. We initially assessed the circulating levels of tumour necrosis factor alpha by ELISA in 20 patients with active Crohn's disease, ten patients with active ulcerative colitis, and ten healthy volunteers. Circulating levels of tumour necrosis factor alpha did not differ significantly between patients (median 80 pg/ml, range 0-2.375) and healthy volunteers (median of 0 pg/ml, range 0-780) (p = 0.16). If a limit of 40 pg/ml was applied, 21 of 30 patients had abnormal values compared to three out of ten controls (p = 0.06), and for the subgroup of patients with Crohn's disease, there was a significantly higher number of abnormal values as compared to controls (p < 0.05), whereas no such difference was found for ulcerative colitis. A parallel study of ten Crohn's disease patients suggested that this result was not explained by differences in circulating tumour necrosis factor alpha inhibitor levels of tumour necrosis factor alpha were measured in 31 patients with active chronic inflammatory bowel disease, 16 with Crohn's disease and 15 with ulcerative colitis. Very low mucosal tumour necrosis factor alpha values were detected in only three patients. Taken together, these results suggest that increased production of tumour necrosis factor does not play a major role in the pathogenesis of chronic inflammatory bowel disease.