BACKGROUND The pathogenesis of chronic idiopathic urticaria is characterized by defective histamine release. Skin mast cells show an increased release of histamine while circulating basophils are less responsive to immunologic stimulus. OBJECTIVE The purpose of the study was to examine and compare the production of the histamine-releasing factor in the skin and within the peripheral blood of patients with chronic idiopathic urticaria and normal control subjects, as a possible factor responsible for the difference observed in the releasability of both skin mast cells and basophils. METHODS Using the skin chamber technique, histamine-releasing factor production and histamine concentration were assessed in normal-appearing skin of patients with chronic idiopathic urticaria (n = 12) and normal controls (n = 5) over a 2-hour observation period. In both groups, histamine-releasing factor production by peripheral blood mononuclear cells was also measured. RESULTS The weighted average of histamine-releasing factor production during the 2-hour observation period was higher in the non-lesional skin of patients with chronic idiopathic urticaria as compared with normal controls (5.6 +/- 1.4% versus 0.7 +/- 0.6%, P < .01). In contrast, less histamine-releasing factor was produced by peripheral blood mononuclear cells in chronic urticaria as opposed to normal controls (17.2 +/- 2.1% versus 25.7 +/- 2.8%, P < .03). Spontaneous histamine concentration was not significantly different in patients with chronic urticaria than in normal controls. CONCLUSIONS Histamine-releasing factor production is increased in the skin, and decreased in the peripheral blood of patients with chronic idiopathic urticaria when compared with nonatopic controls. The lower production of histamine releasing factor in the blood could be explained by the migration of activated T-lymphocytes in the skin.