We investigated the acute effect of ascorbic acid on histamine bronchial responsiveness (PC 20: concentration causing a 20% fall in FEV1) in 9 hospital staff members with upper respiratory tract infection (URI) and cough. Subjects were examined within 5 days from the start of illness and 6 weeks after. On day 1, the reproducibility of PC20 was assessed by 2 consecutive inhalation challenges 1 h apart; the two values were closely related (r = 0.96, p less than 0.001). Five subjects had bronchial hyperresponsiveness (PC20 less than 8 mg/ml histamine). On the following day, PC20 was measured before and 1 h after oral intake of 2 g ascorbic acid. Vitamin C produced a significant increase in average PC20 (p less than 0.01) from 7.8 +/- (SE) 1.2 to 25.1 +/- (SE) 1.2 mg/ml. None had airway hyperresponsiveness after treatment. Six weeks after the onset of URI, bronchial responsiveness was normal in all the subjects but one. The mean PC20 was 15.5 +/- (SE) 1.25 mg/ml, significantly higher than during URI (p less than 0.05); after ascorbic acid it increased nonsignificantly to 25.7 +/- (SE) 1.35 mg/ml. Our results indicate that vitamin C inhibits the transient increase in bronchial responsiveness occurring in otherwise normal subjects during URI.