New knowledge of adverse external ocular reactions to topical ophthalmic medications was obtained by means of a computerized epidemiologic study, laboratory studies, and clinical observations. Listed below are the major findings and conclusions that represent facts or concepts that were previously unknown, uncertain, misunderstood, or forgotten: The incidence of clinically important drug reactions among all cases was at least 13.09% and may have been as high as 16.02%. Among treated patients it was at least 16.26% to 19.90%. Taken together, drug reactions were the second most common external disease diagnosis. The incidence of each kind of drug reaction was determined. Toxic papillary reactions accounted for 79.10% of drug cases and 10.35% of all cases. Toxic papillary keratoconjunctivitis was the third most common single diagnosis. The following epidemiologic factors were found to be related to the development or presence of drug reactions: number and variety of treating practitioners, number of practitioners consulted, number of practitioners consulted who treated, specific ophthalmologist consulted (8.24% of ophthalmologists referred 39.55% of all drug cases and showed a tendency habitually to overtreat), number and kinds of patients' symptomatic complaints, number of medications prescribed and used, number of days of treatment, particular drugs and preservatives used (but not their strengths or vehicles), underlying (primary) diagnoses, and inaccuracy of referring ophthalmologists' diagnoses. Patients with dry eyes were especially at risk for the development of toxic papillary reactions. Among all cases, the incidence of reactions to preservatives (mainly thimerosal) in contact lens solutions was 0.39% to 1.95%, depending on whether definite or probable cases, respectively, were considered. The incidence among the 54 patients who used daily-wear lenses (excluding extended-wear therapeutic and optical contacts) was 7.41% for definite reactions and 37.04% for probable ones. Factors relating to the development of papillary contact-lens reactions were daily wear, number of days of wear, and, especially, the preservatives to which the patients were exposed. Reactions occurred more often with soft lenses than with hard ones. Of patients with drug reactions, 5.22% had two different ones simultaneously. Coexisting reactions to pharmacologically active agents were also present in 15% of patients who reacted to preservatives in contact lens solutions. The ocular tissues that were affected by each kind of drug reaction were tabulated, and the relative degrees and sequences of involvement were discussed. The frequencies with which particular drugs, physical ag