The importance of parasympathetic-cholinergic mechanisms in the production of common cold symptoms is not clear. The quaternary ammonium anticholinergic antagonist ipratropium bromide was intranasally administered under double-blind, randomized, placebo-controlled conditions to assess its tolerance and efficacy in reducing nasal hypersecretion in adult volunteers with experimental rhinovirus colds. Ipratropium was sprayed intranasally three times daily (80 micrograms per treatment) for 5 days beginning 24 h after intranasal inoculation of rhinovirus type 39. Clinical colds occurred in 50% of 30 infected ipratropium recipients and in 76% of 33 infected placebo recipients (P = 0.04). The nasal mucus weights tended to be lower for ipratropium-treated persons (mean +/- standard deviation, 14.7 +/- 15.1 g/5 days) than for placebo-treated recipients (24.7 +/- 28.0 g/5 days; P = 0.076). Whereas total nasal symptom scores were similar between the two groups, the rhinorrhea score analyzed for each day of treatment showed nonsignificant trends favoring the ipratropium group over the last 4 days of treatment. Ipratropium was generally well tolerated. The results suggest that cholinergic mechanisms are at least partially responsible for nasal mucus production in rhinovirus colds but that the effect of anticholinergic compounds alone is insufficient to be of practical use in treatment, although they may have value as components of multi-ingredient preparations.