We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial investigating the use of topical human fibroblast interferon (HuIFN-beta) 7.5 x 10(5) IU/ml, one drop 5 times daily, in the treatment of acute epidemic conjunctivitis. Of 50 patients who were initially enrolled, tear-film cultures for adenovirus were positive from 26% for type 8, 12, or 19. Based upon a quantifiable conjunctivitis severity score of 37 patients evaluated after approximately 1 week of therapy, analysis of covariance showed a statistically significant greater improvement with topical HuIFN-beta compared with placebo for affected left eyes (P = 0.02) but not for right eyes (P = 0.5), an effect that could not be adequately explained. We suggest that a higher dosage of topical HuIFN-beta may prove useful in the control of more severely affected cases. This trial provides guidelines for future investigations of interferon in the treatment and prophylaxis of adenoviral keratoconjunctivitis.