Nasal administration of an interferon inducer, CP-20,961 (N, N-dioctadecyl-N\', N\'-bis(2-hydroxyethyl)propanediamine), was evaluated in a double-blind, placebo-controlled study of experimental rhinovirus infection in 29 volunteers. Detectable nasal interferon developed in 10 of 15 subjects treated with CP-20,961, and 2 of 14 in the group receiving placebo (P < 0.006). Titers of CP-20,961-induced interferon ranged from 10 to 250 international units, concentrations similar to those observed in rhinovirus infections. Ten in the CP-20,961 group and eight in the placebo group became ill (P > 0.05). However, mean total sign scores were significantly diminished among CP-20,961-treated subjects as compared with placebo-treated subjects (P < 0.025). No significant effect was noted on quantitative virus shedding patterns or neutralizing antibody responses. These findings suggest that such concentrations of induced interferon do not protect against rhinovirus infection, and that factors other than interferon may be important in recovery from rhinovirus infection.