To determine the safety and effectiveness of low-dose oral interferon-alpha (IFN-alpha) against measles, 30 confined pediatric patients were prospectively and randomly assigned to either a placebo or an oral IFN-alpha group and observed daily for 14 days in a double-blind manner. The IFN patients received a daily sublingual dose of 200 IU of human lymphoblastoid IFN-alpha. The IFN-treated group showed shorter average duration of malaise (3.2 vs. 10.7 days, p < 0.0001), anorexia (3.1 vs. 6.7 days, p < 0.0001), and irritability (1.1 vs. 2.2 days, p < 0.01) and shorter duration of macular/maculopapular/papular lesions (4.3 vs. 8.2 days,p < 0.0001) and branny desquamation (4.6 vs. 5.8 days, p > 0.05) and shorter time for rash to become generalized (5.5 vs. 10.3 days, p < 0.0001). No hematologic, renal, or liver toxicities were noted. It, therefore, appears that low-dose oral human lymphoblastoid IFN-alpha used in this pilot study is both safe and effective in children with measles infection.