The possibility of synergistic effects among various drugs used in treating hypertension was explored by testing four combinations: hydralazine and reserpine (18 patients), hydralazine and pentolinium (6), reserpine and pentolinium (30), and all three drugs (24). The dosages varied somewhat, since an effort was made to increase the intake of each drug to reasonable tolerance. The drugs had been used singly in previous studies. The present study indicated the effectiveness of hydralazine when combined with reserpine for treatment of hypertension of moderate severity. Mean blood pressures, as measured in the recumbent position, fell to normal in 11 (61 %) of the 18 patients in this group, and the only major drug reaction in this group was hydralazine arthritis in one patient. The combination of hydralazine with reserpine was found to be simple, easily employed in outpatients, and relatively free from intolerable side-effects, provided that the dosage of each drug is gradually adapted to the tolerance of the patient. Hypertensive disease when present in the severe form generally requires the addition of a blocking agent to the combination of reserpine and hydralazine.