BACKGROUND Interferon-gamma (IFN-gamma) is a potent cytokine that modulates IL-4-induced immune responses. Atopic dermatitis is associated with increased IgE levels and decreased IFN-gamma production. Recent phase I and phase II studies have suggested that short-term rIFN-gamma therapy is effective in the treatment of severe atopic dermatitis. OBJECTIVE We evaluated the safety and efficacy of long-term use of rIFN-gamma for severe atopic dermatitis. METHODS Fifteen patients were treated for a minimum of 22 months with 50 micrograms/m2 rIFN-gamma qd or qod. Patients were monitored every 3 months for safety, efficacy, and linear growth in pediatric patients. RESULTS Data represented a total of 47 patient years, which included 29 pediatric patient years. There was a statistically significant decrease in mean total body surface area involvement over time (P < .001, ANOVA). Mean total body surface area involvement was 61.6% at baseline and decreased to 18.5% at 24 months (P < .001). Likewise, there was a statistically significant decrease in the clinical severity parameters. The mean total clinical severity score was 11.4 at baseline and decreased to 6.3 at 24 months (P < .001). Statistically significant decreases in WBC, neutrophil counts, and eosinophil counts were observed compared with baseline counts. No other significant laboratory abnormalities or growth problems were seen. CONCLUSIONS We conclude that rIFN-gamma appears to be a safe long-term therapy for patients with severe atopic dermatitis.