An antiviral agent and two antiinflammatory compounds were used in a blinded, placebo-controlled study to treat experimental rhinovirus colds. Intranasal interferon-alpha 2b and ipratropium and oral naproxen were begun 24 h after rhinovirus inoculation. Treatment was continued three times a day for 4 days. Viral shedding (mean +/- SE) was 4.4 +/- 0.3 days for controls and 2.9 +/- 0.3 days for treated volunteers (P less than .003). Geometric mean virus titers were reduced in the treated group on all days (P = .02-.06). Serum antibody responses and postinfection geometric mean antibody titers were similar in both groups (P greater than .1). Colds developed in 6 of 16 treated and 7 of 8 control subjects (P = .05). Mean total symptom scores (P = .055), rhinorrhea (P less than .01), cough (P less than .01), and malaise (P less than .001) were reduced in treated subjects. Trends in reduction of nasal obstruction and sore throat also favored the treated group. Nasal secretion weights were 12.9 +/- 4.8 g in treated and 20.3 +/- 5.4 g in control subjects (P = .4). Medications were was tolerated.