Serum interferon (IFN) of alpha-class was studied in 64 consecutive patients, 26 with Crohn's disease, 38 with ulcerative colitis, and in 34 healthy volunteers. Detectable IFN-alpha in 10 patients was associated with a moderate to severe activity of chronic inflammatory bowel disease (CIBD). However, 19 of 28 patients (68%) with activity in their disease did not have elevated IFN-alpha levels. The three groups, ulcerative colitis, Crohn's disease, and healthy volunteers did not reveal any statistically significant difference in serum IFN-alpha, as four of 34 healthy controls without intercurrent infections had elevated levels as well. Possible effects of alpha, beta, and gamma classes of IFN on endogenous arachidonic acid (AA) release and metabolism in human neutrophils was investigated in a substudy. IFN-alpha caused a dose-dependent release of AA from phospholipids and metabolism of a modest fraction of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) at doses reaching a maximum of 100 IU/ml. IFN of the beta and gamma classes did not exert such effects. Addition of complement 5a to cells activated by IFN-alpha caused induction of increased 5-lipoxygenase activity with unchanged release of AA. As only 16% of all CIBD patients had elevated IFN-alpha levels as compared to 12% among the group of healthy volunteers, IFN-alpha does not seem to be of importance for the perpetuation of the inflammatory reaction in ulcerative colitis or Crohn's disease, and other factors may therefore be responsible for activation of the inflammatory cells to production of LTB4 and 5-HETE.