To assist in identifying pathogenetic mechanisms in different clinical manifestations of cow's milk allergy (CMA), the involvement of eosinophil cells in immunoinflammatory reactions was evaluated. The study population comprised 28 patients, aged from 5.8 to 43.0 months, who had challenge-proven CMA, manifested either cutaneously (n = 17) or gastrointestinally (n = 11). A clinical cow's milk challenge was performed in hospital after a 4 week cow's milk elimination period. Eosinophil activation in vivo was studied by measuring the serum level of eosinophil cationic protein (ECP) before the oral cow's milk challenge, mean (SD) 27 (12) hours after commencing the challenge and one week later. These results were compared to those of 80 non-allergic age-matched controls. During the challenge, the level of ECP increased from 6.2 (4.5, 8.0) micrograms/L to 20.0 (9.5, 30, 4) micrograms/L in CMA patients with skin manifestations but not in those with gastrointestinal symptoms. The increase was shown to be transient. We conclude that eosinophil degranulation is an important immunologic mechanism leading to allergic inflammation in cutaneously manifested CMA.