Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by various immunologic abnormalities. We have studied the efficacy of recombinant human interferon gamma (rhINF-gamma) administered subcutaneously at a dose of 0.05 mg/m2 in ten patients with severe AD. Patients were treated for 4 weeks. They have shown marked clinical improvement starting from the third week of treatment. The efficacy of the drug varied, with erythema, dryness and lichenification being the most responsive symptoms. There was no change in serum immunoglobulin E and IgG4 levels. Whole blood eosinophil count decreased only transiently and was accompanied by a tendency to lower values of serum eosinophil cationic protein. Patient with AD showed an increased expression of a T-cell surface activation marker CD 25 as compared to healthy controls. Moreover, clinical improvement was roughly paralleled by the decrease in this T-cell activation marker. We conclude that rhINF-gamma is a novel efficacious therapeutic approach in severe AD. We suggest that its primary action might be related to the inhibition of T-cell activation.