A double-blind crossover study to determine the effects on intraocular pressure (IOP) and blood pressure of topically instilled 0.125% and 0.25% solutions of clonidine hydrochloride by comparison with a 2% pilocarpine hydrochloride solution and placebo was carried out in a total of 21 patients with open-angle glaucoma, each of whom received a single drop of each preparation in the same glaucomatous eye on separate days. Both clonidine solutions were effective in lowering the IOP; the 0.25% solution was more effective than the 0.125% solution, and the former was slightly less potent than pilocarpine. Pupil diameter was essentially unchanged in all but one of the patients after clonidine. Pilocarpine reduced pupil diameter in all patients. One eye treated with placebo also showed a reduction in pupil size. Both systolic and diastolic blood pressure showed a statistically significant reduction after clonidine, but the magnitude of the change was small. We do not regard the minor blood pressure changes as being a threat to the optic nerve but further studies in this aspect of topical clonidine therapy are required.