We have examined the response of lumbar dorsal horn cells to a noxious mechanical stimulus during differential delivery of isoflurane to the brain and spinal cord of goats. We hypothesized that isoflurane, acting in the brain, would depress dorsal horn neuronal responses to a noxious mechanical stimulus applied to the hindlimb. Eight goats were anaesthetized with isoflurane and neck dissections performed which allowed cranial bypass. Lumbar laminectomies were performed to allow measurements of single-unit dorsal horn neuronal activity. Isoflurane 1.3% was administered before bypass, and during differential delivery it was administered at each of the following head/torso combinations: 1.3%/1.3%, 0.8%/1.3%, 0.3%/1.3%, 1.3%/0.8%, 0.8%/0.8% and 0.3%/0.8%. When the torso isoflurane concentration was 1.3%, decreasing cranial isoflurane from 1.3% to 0.3% did not significantly affect dorsal horn responses (from mean 325 (SD 262) to 379 (412) impulses min-1; P < 0.05). However, when torso isoflurane was 0.8%, decreasing cranial isoflurane from 1.3% to 0.3% increased mean evoked dorsal horn activity by 42% (388 (359) to 551 (452) impulses min-1; P < 0.05). These data suggest that the major effect of isoflurane on dorsal horn responses to noxious stimuli is direct, but there is an indirect effect occurring via descending projections from supraspinal regions.