Effects of electrical stimulation of the periventricular gray (PVG) on spinothalamic tract (STT) cell activity were determined in 19 anesthetized monkeys (Macaca fascicularis). Twenty-two STT cells projected to the ventral posterior lateral nucleus (L-STT cells), 11 to the medial thalamus (M-STT cells), and 9 to both thalamic regions (LM-STT cells). All cells had somatic receptive fields and responded to electrical stimulation of cardiopulmonary sympathetic afferent fibers. PVG stimulation inhibited activity of 41 of 42 STT cells. Degree of inhibition of background activity was related to intensity and frequency. Stimulus currents of 300 microA or less completely silenced background activity of most cells. Thresholds for stimulus current averaged 100 +/- 20 microA and were unrelated to cell projection site, laminar location, or type of somatic or visceral input. However, lowest thresholds were found when the PVG electrodes were located within 0.5 mm of the third ventricle in the dorsomedial hypothalamus or nucleus reuniens of the thalamus. PVG stimulation inhibited responses of 22 of 22 cells to intracardiac injections of bradykinin. Bradykinin (2 micrograms/kg) increased cell activity from 15 +/- 3 to 31 +/- 5 spikes/s (P less than 0.01), and PVG stimulation (380 +/- 40 microA) reduced activity to 9 +/- 3 spikes/s (P less than 0.001). PVG stimulation inhibited responses of 33 of 33 STT cells to noxious pinch of skin or skin and muscle and responses of 8 of 8 cells to hair movement. Degree of inhibition of cell responses to noxious pinch was not significantly different from inhibition of responses to bradykinin. Effects of PVG stimulation on activity of six STT cells were studied before and after bilateral lesions were made in the dorsolateral funiculus (DLF). In no case did the lesions abolish or attenuate inhibitory effects of PVG stimulation. These results suggest that PVG may participate in descending inhibition of STT cells including cells mediating cardiac pain. The descending pathways are not located in the DLF. Further, descending inhibitory systems modulate STT cells projecting to both medial and lateral thalamus.