The purpose of this study was to monitor histamine release in immediate-type hypersensitivity reactions in the skin of 10 atopic patients, sensitive to cow, by using the microdialysis technique. Three healthy subjects, without any atopic features or background, served as the control group. The probe inserted into the forearm dermal skin was perfused with isotonic saline solution. Samples were collected at 15-min intervals. After the first allergen challenge of four prick tests close to the probe with cow allergen extract, the skin was similarly repricked again in five patients and three healthy subjects, and in five other patients, 25 microliters of 10 mumol/l substance P (SP) was injected intracutaneously. The samples were analysed for histamine by radioenzyme assay. The patients were clinically evaluated for allergic symptoms, prick- and scratch-patch test reactivity and for serum cow-specific, and total, IgE levels. The baseline histamine concentration was 7.5 +/- 4.0 nmol/l (mean +/- standard deviation: SD; n = 10). After the allergen challenge, the histamine concentration in the consecutive samples was 11.9 +/- 11.0 nmol/l, 91.1 +/- 127.3 nmol/l, 61.0 +/- 94.2 nmol/l and 33.7 +/- 53.7 nmol/l. The peak concentration was detected in the 15-30 min fraction, and it varied between 0 and 406 nmol/l regardless of the weal size. The second allergen challenge was unable to induce marked additional histamine release, but SP induced extensive histamine liberation in those patients who did not exhibit histamine release during the preceding prick tests. In three healthy subjects, the baseline histamine concentration was 6.2 +/- 3.9 nmol/l. After the allergen challenge, no additional histamine liberation could be measured. Surprisingly, the histamine release was not related to the size of the cow-induced weal nor was it related to any specific allergic symptoms or IgE levels. The results suggest that, in some patients, mast cell mediators other than histamine play a significant part in immediate-type allergic reactions of skin.