To determine whether the cough of the common cold arises from upper respiratory stimuli and whether antihistamine-decongestant therapy is an effective treatment for this cough, we prospectively evaluated volunteers with uncomplicated common colds in a randomized, double-blind, placebo-controlled study. After completing a standardized questionnaire and undergoing a physical examination, throat-culturing, and pulmonary function testing, subjects took the active drug or identical-appearing placebo for 7 days while they kept a diary in which they ranked the severity of 17 symptoms for 14 days. Pulmonary function testing was repeated, on average, on Days 4, 8, and 14. Forty-six percent of the variation in cough severity could be explained by throat-clearing and 47% of the variation in throat-clearing severity by postnasal drip. FIF50%, the only physiologic parameter that significantly correlated with cough, rose as cough severity fell. Antihistamine-decongestant therapy reduced postnasal drip and significantly decreased the severity of cough, nasal obstruction, nasal discharge, and throat-clearing during the first few days of the common cold. In addition, cough was 20 to 30% less prevalent in the active drug group within 3 days of starting therapy. We conclude that the cough of the common cold arose from upper respiratory tract stimuli and that cough and other cardinal symptoms of the common cold were reduced with antihistamine-decongestant therapy when these symptoms were at their worst.