The prophylactic effect of recombinant leukocyte A interferon (rIFN-alpha A) (dosage, 10 X 10(6) units per day for four days) against illness and infection in 26 volunteers challenged with rhinovirus type 13 was measured in a double-blind, placebo-controlled study. Significant reductions in illness frequency (7.1% vs 66.7%, P less than 0.003), mean symptom scores, nasal secretion weights, and frequency of virus isolation were observed. However, there was no significant difference in infection rates between rIFN-alpha A- and placebo-treated volunteers. Late posttreatment virus shedding, which was unassociated with late illness, was observed in the rIFN-alpha A-treated group. In two double-blind, placebo-controlled tolerance studies of rIFN-alpha A, five (26%) of the 19 volunteers treated with rIFN-alpha A reported bleeding mixed with mucous nasal discharge and had documented superficial erosions of the nasal mucosa. Future studies will be necessary to evaluate lower doses and/or alternative treatment schedules for improved tolerance and continued efficacy.