We used a rhinovirus challenge model to test the therapeutic efficacy of clemastine fumarate for reducing sneezing and nasal secretion in a double-blind, randomized clinical trial. Clemastine fumarate (1.34 mg) or placebo was administered at 8 A.M. and 8 P.M. for 4 days, beginning 24 hours, 36 hours, 48 hours, and 60 hours after viral challenge. Infected evaluable subjects who received clemastine (n = 75) had reduced sneeze-severity scores compared with those who received placebo (n = 75) on illness days 2 (0.3 vs. 0.5; P = .003), 3 (0.4 vs. 0.8; P = .0003), 4 (0.3 vs. 0.5; P = .025), and 5 (0.1 vs. 0.3; P = .03); sneeze counts for infected evaluable subjects (vs. counts for those who received placebo) were reduced on illness days 2 (1.5 vs. 3.1; P = .01), 3 (1.7 vs. 5.6; P = .0001), and 5 (0.7 vs. 1.9; P = .03). Infected evaluable subjects who received treatment had reduced rhinorrhea scores (compared with those who received placebo) on illness days 2 (0.7 vs. 1.0; P = .04) and 3 (0.6 vs. 0.9; P = .04) and had reduced nasal secretion weights on day 3 (3.6 g vs. 6.3 g; P = .03). Over 4 days of treatment, mean sneeze scores for infected evaluable subjects (vs. scores for those who received placebo) were reduced by 50%, mean sneeze counts by 57%, mean rhinorrhea scores by 27%, and mean nasal secretion weights by 35%. Other cold symptoms were unaffected by treatment. Treatment with clemastine was associated with an excess incidence of dry mouth (6%), dry nose (19%), and dry throat (17%).