A long term study was undertaken to evaluate the efficacy of combined guanethidine (1%) and adrenaline (0.05-0.5%) therapy in controlling intra-ocular pressure in 89 patients with chronic open angle glaucoma, in whom ocular tensions proved difficult to control on miotics and/or carbonic anhydrase inhibitors. Visual acuity, fields of vision, applanation tension, size of the pupil, anterior chamber depth and gonioscopic examination of the angle were recorded before and during treatment. The follow-up extended over a period of 12 to 42 months, the mean being 28 months. The combined therapy was found to lower the intra-ocular pressure significantly in a large number of patients and the most potent combination was guanethidine 1% and adrenaline 1/4% and the average fall of intraocular pressure with the combined therapy was around 8 mm Hg. Intolerance to the combined preparation was noticed in three patients during a period of 12-18 months with the symptoms of sore eyes, conjunctival hyperaemia and lid irritation of such severity that the treatment had to be withdrawn. Resistant to treatment developed in four patients during a period of 12-36 months and treatment had to be changed. Addition to guanethidine (1%) and adrenaline up to 1/4% to pilocarpine therapy (2-4%) in eyes with narrow angles did not result in any appreciable change of the width of the angle, the size of the pupil and the depth of the anterior chamber.