Undesirable side effects have limited the use of adrenaline/guanethidine combinations in the usual concentrations in the treatment of chronic simple glaucoma. Better tolerance to lower concentrations has already been demonstrated in other studies. In the double-blind study described here, three different combinations (adrenaline 1%, 0.5% and 0.2% combined respectively with guanethidine 5%, 3% and 1%) were compared in respect of their depressive action on intraocular pressure and the tolerance shown to them. All three combinations were found to be effective. The combination with the lowest concentration was significantly less hypotensive in its effect than the other two but the number of patients treated was too small to allow a clear distinction to be made between the effects of the other two combinations. Nevertheless, there was a tendency for the effectiveness to fall with decreasing concentration. As far as tolerance was concerned, there was little difference between the middle and lowest concentrations, the latter being that best tolerated. The excellent effect of the strongest concentration was impaired by the poor tolerance shown to it. The comparison between the three combinations was followed by a study of the diurnal pressure changes in patients during the course of the treatment. The slow rise up to midday and the abrupt afternoon fall remain unexplained. The low concentration of the preparation had a better hypotensive action than pilocarpine, while the middle concentration proved even a little better than the beta-blocker Timolol