PURPOSE: We performed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of 0.12% zinc sulfate nasal spray for reducing the duration and severity of acute upper respiratory infections. SUBJECTS AND METHODS: Patients with acute onset of upper respiratory illness of less than 24 hours\' duration were eligible for the study. A nasopharyngeal swab was obtained at the time of enrollment for viral culture. Participants were randomly assigned to receive either 0.12% zinc sulfate or isotonic placebo spray. The medication was administered as two inhalations in each nostril four times a day. Each patient completed a diary card twice a day to record oral temperature, symptoms, and adverse effects. Symptoms were scored as absent (0), mild (1), moderate (2), or severe (3). RESULTS: One hundred eighty-five subjects volunteered to participate, and 160 met the criteria for enrollment. The median duration of all symptoms was 7 days in both groups (P = 0.45), and the median duration of nasal symptoms was 6 days in both groups (P= 0.12). After adjustment for baseline differences in severity, patients receiving zinc had a significant reduction in the total symptom score (P= 0.02) and the nasal symptom score (P= 0.02) on day 1, but not on any of the other days. Adverse effects were mild and had no significant association with the use of zinc. A respiratory virus was identified in 9 of the 160 participants; 6 of these were rhinovirus. CONCLUSION: A low concentration of zinc sulfate nasal spray had no effect on the duration of the common cold.