Antihypertensive drugs with pharmacological action due to sympatholytic activity have been second only to diuretics in their use and efficacy in normalizing blood pressure. Their pharmacological actions have resulted in the notable absence of chemical toxicity, but because of symptomatic side effects, their use has been limited relative to some of the newer antihypertensive agents. Most prominent among undesirable side effects are the central nervous system findings of sedation, altered thought process, depression, and orthostatic or exercise hypotension. Sexual problems, especially in men, are also prominent. Special toxicity is discussed with reference to methyldopa, clonidine, monoamine oxidase inhibitors, and metyrosine.