The effects of the antispastic drug, baclofen, were examined in sympathetic preganglionic neurons (PGNs) recorded in the isolated spinal cord of the neonatal rat. Addition of 10(-5) M baclofen to the superfusion medium inhibited the activation of PGNs by dorsal root stimulation in 96% of the neurons tested. The time course of inhibition of sympathetic reflexes paralleled the inhibition of ventral root (primarily somatic) reflexes evoked by the same stimulus. Spontaneous activity was abolished by baclofen in 69% of the spontaneously active PGNs tested. It is concluded that baclofen has a powerful sympatho-inhibitory effect at the spinal level.