The role of histamine in the pathogenesis of infectious rhinitis is unclear, as is the efficacy of antihistaminic drugs in the treatment of the common cold. This study evaluated the short-term efficacy of oral terfenadine (Seldane) in the treatment of the common cold. Over a 5-week period, the authors recruited 250 adults who had developed cold symptoms within 6 to 48 hours prior to enrollment. Volunteers had a primary complaint of runny or stuffy nose; at least one other respiratory symptom; no fever or exudative pharyngitis; and no history of atopy, sinusitis, or use of cold preparations within 1 week of enrollment. Out of the eligible subjects, 126 were randomly assigned terfenadine (60 mg), and 124 received placebo. Volunteers self-administered either terfenadine or placebo twice a day on Days 1, 2 and 3, and a final dose on the morning of Day 4. They also recorded the severity of their clinical symptoms (runny nose, sniffles, sneezing, postnasal drip, cough and sore throat) on symptom cards. Both groups reported similar severity scores throughout the treatment period. Average symptom burdens declined at almost identical rates for both groups. Terfenadine was well tolerated and had a low incidence of side effects. According to subject evaluation, terfenadine was no more effective than placebo. The mean +/- SD score of global efficacy was 2.2 +/- 1.1 in the terfenadine group and 2.1 +/- 1.3 in the placebo group (P = NS). Slightly fewer terfenadine recipients (41%) than placebo recipients (48%) said they would use the study medication again for treating cold symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)