In two placebo-controlled, double-blind studies, the prophylactic efficacy of recombinant DNA-produced interferon alpha 2 (IFN-alpha 2) against induced rhinovirus (RV) type 39 infection in susceptible volunteers was assessed. IFN-alpha 2 was given by intranasal drops in either multiple treatments (11.4 X 10(6) IU four times per day for four days) or one treatment daily (42.8 X 10(6) IU once per day for five days) starting before RV type 39 challenge. The efficacy rates of multiple-dose IFN-alpha 2 for preventing infection, virus shedding, and RV type 39-specific colds were 78%, 78%, and 100%, respectively. The corresponding rates for one daily treatment were 45%, 64%, and 75%, respectively. Both dosage regimens were associated with significant reductions in days of virus shedding and nasal mucus production. In the second study, three IFN-alpha 2 recipients developed transient leukopenia (less than 4,000 leukocytes/mm3). The results suggest that intranasal IFN-alpha 2 may prove to be a safe and effective method of preventing rhinovirus infection and illness.