Eighteen healthy volunteers participated in a histamine challenge, dose response study of cimetidine (H2 antagonist)/pyrilamine (H1 antagonist) eyedrops. This was a randomized, double-masked, multiple-crossover trial, consisting of six visits spaced 48 hours apart. At each visit, subjects were pretreated with one of six different doses of test medication in one randomly selected eye and with vehicle in the fellow eye. Five minutes later, one drop of 0.0075% histamine was instilled in both eyes. Conjunctival hyperemia and edema were graded at various time points during a 20-minute interval after the instillation of histamine. Results indicated that the cimetidine/pyrilamine combination was effective in preventing histamine-induced conjunctival hyperemia in normal volunteers; neither cimetidine nor pyrilamine was effective when administered alone.