The study of the ocular adrenergic systems at the Wilmer Institute over the last 40 years began with the examination of the formation and outflow of aqueous humor by Jonas Friedenwald and his co-workers in the early 1940's. At that time, researchers were attempting to understand the mechanisms of fluid dynamics in the eye, with the idea of altering these mechanisms to alleviate glaucoma only a distant goal. In the late 1950's, Langham and others reported on the effect of superior cervical ganglionectomy on intraocular pressure, following this work with a succession of papers on the relationship between alpha and beta adrenergic substances and aqueous humor dynamics. Sears, in collaboration with Bárány, described the effects of alpha and beta adrenergic substances on outflow resistance. Eakins, in 1963, suggested a mechanism of action for isoproterenol in the lowering of intraocular pressure. Work on timolol at Wilmer began with a report from Radius, Diamond, Pollack and Langham covering experimental studies with rabbits and clinical studies of the drug's ocular hypotensive effects on glaucoma patients. Richter and others also studied a small number of patients on maximal therapy and found further intraocular pressure reduction with added timolol. © 1979.