Double-blind trials were conducted in volunteers to evaluate the efficacy of the prophylactic 3,4-dihydro-1-isoquinolineacetamide hydrochloride (DIQA) treatment against rhinovirus type 24 challenge. Ten men received a 7-day course of DIQA treatment and 11 men received a placebo. The intranasal viral challenge dose was 10 mean tissue culture infective doses. The oral administration of 1 g prechallenge and 2 g a day for 6 consecutive postchallenge days did not prevent the development of colds. Nine drug-treated men and 10 controls developed rhinovirus illness. However, the illnesses of the drug-treated men were mild. Rhinorrhea occurred less frequently and was more mild in the drug-treated group. The challenge virus was recovered from 80% of these subjects in both groups, but almost twice the number of challenge viruses were isolated from the controls than from the drug-treated men. The prophylactic DIQA therapy appears to suppress the cold syndrome and to reduce virus excretion, although its effect is marginal. Additional clinical trials are warranted to confirm the antirhinoviral effect of this drug.