The older Indian literature records the liberal use over several centuries of preparations of the roots of Rautwolfia species, and particu!arly Rauwolfia serpentina, for the treatment of dysentery, snakebites, and fever (? malaria). In more recent times these preparations have been used in India as sedatives and also for insomnia and insanity. By the end of the seventeenth century this use of rauwolfia root as a sedative had apparently reached Europe. The genus Rauwolfia belongs to the Apocynaceae and contains some 40 to 50 species, but R. serpentina, a large twining shrub found in India and Malaya, appears to be the main member used for these purposes, and it is therefore this plant whose roots were credited with all these most desirable qualities.Preparations of these roots of R. serpentinia were found to have definite hypotensive properties when tried in animals (Chopra et al., 1933) in addition to producing hypnotic and sedative effects. This hypotensive action on the blood pressure has apparently been confirmed in varying degree in hypertensive patients (Vakil, 1940(Vakil, , 1949 Bhatia, 1942;Wilkins and Judson, 1953; Ford et al., 1953: Arnold andBock, 1953 ;Klausgraber, 1953 Joiner andKauntze, 1954).The hypotensive and hypnotic action of preparations of R. serpentina root would appear to reside in the content of alkaloids, of which some 15 have so far been isolated, two of the most active of these being rescinnamine and reserpine, ester alkaloids chemically ielated to yohimbine, differing only in the acid moiety (trimethoxycinnamic and trimethoxybenzoic acid). Reserpine makes up about 0.1% of crude preparations, and would seem in man to be more likely to cause drowsiness and diarrhoea than rescinnamine. In dogs it has only half the hypotensive potency (Cronheim and Toekes, 1955), but there is a marked variation in relative activity of these alkaloids in different animal species. There would also appear to be at least one other, as yet unidentified, highly active alkaloid in the crude extract.Since, experimentally, rauwolfia does not interfere with transmission at the autonomic ganglia and in therapeutic dosage is neither adrenolytic nor sympatholytic, it has been suggested that the hypothalamus is the site of its activity, but this has not been proved.Our past experience when using recommended hypotensive agents given by mouth for the treatment of essential hypertension had been most unsatisfactory.When rauwolfia became available two years ago it was therefore decided that a carefully controlled trial was essential. A prolonged periqd of observation by observers, if possible unchanged during the trial, of a suitable series of hypertensive patients in need of treatment, using each patient as his own control, would, it was felt, be most likely to yield,results of any value at this stage of our knowledge of the treatment of hypertension.