The effect of intralesional alpha 2-interferon (IFN) on actinic keratoses was examined in this two-part study. In phase I, 11 of 12 lesions cleared following nine injections of IFN (5 X 10(5) IU per dose) compared with none of 12 keratoses injected with placebo. Smaller doses of IFN (1 X 10(5) IU and 1 X 10(4) IU per injection) produced clearing of 42% and 58% of lesions, respectively. The second phase, which was designed to investigate the optimum schedule for treatment with IFN, showed that a minimum of six injections of IFN (5 X 10(5) IU per injection) was necessary to clear 14 of 15 actinic keratoses. Although this mode of delivery is not practical for clinical use, intralesional alpha 2-IFN demonstrates biologic activity against actinic keratoses.