The antihypertensive activity of methyldopa is mediated primarily by effects on the central nervous system. A number of centrally acting hypotensive substances has recently been shown to depress spinal pathways and reflexes as well as inhibiting supraspinal areas. The present series of experiments evaluated the potential influence of methyldopa on spinal mechanisms. Stimulation of an intercostal nerve evoked a two-component response (early and late) in the splanchnic nerve of anesthetized cats. The "late" phase involves supraspinal neurons, whereas, the "early" component involves only spinal pathways. The i.v. administration of 100 mg/kg of methyldopa reduced systemic blood pressure and both components of the evoked potential progressively. These experiments indicate that methyldopa exerts an effect of spinal sympathetic mechanisms which may contribute to the antihypertensive response to the compound.