Single neurons in spinal laminae I and II of cats were recorded intracellularly while stimulating in nucleus raphe magnus (NRM) and periaqueductal gray (PAG) with monopolar tungsten microelectrodes. Brain stem stimulation inhibited about one-half of the nociceptive-specific neurons, whereas the other half was unaffected. Brain stem stimulation inhibited about one-half of the multireceptive neurons, but the other half was excited and then inhibited. Brain stem stimulation inhibited about one-third of the low-threshold neurons, one-half was excited then inhibited, and one-fifth showed no effect. In all classes of neurons, the inhibition was produced by an inhibitory postsynaptic potential (IPSP) that began with a latency of approximately 25 ms and lasted approximately 400 ms following a single stimulus. The IPSP occurred with a small conductance increase and was reversed by hyperpolarizing currents applied to the cell. These data indicate that NRM and PAG modulated laminae I and II neurons via a postsynaptic mechanism. The conduction velocity of this descending pathway was calculated to range from 6.1 to 66.6 m/s with an average of 13.8 m/s. These data also indicate heterogeneity in the pathway, since some neurons were inhibited, whereas other neurons were excited then inhibited by descending stimulation. Finally, these data indicate specificity in these descending pathways since nearly one-half of neurons that had low-threshold inputs were excited by brain stem stimulation, whereas nearly all nociceptive-specific neurons were either inhibited or unaffected.