To study the effects of intrathecal administration of a neurokinin-I(NK-I) receptor antagonist (CP96,345) on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in anaesthetized rats, and on the locomotive activity of conscious rats.Wistar rats (n = 36) were fitted with indwelling intrathecal catheters, and the MAC of isoflurane was determined following the intrathecal administration of saline (control group) or the NK-I receptor antagonist CP96,345 (CP) at 1, 10 and 100 micrograms. Subsequently a reversal dose of intrathecal Substance P (SP) at 1, 10 and 100 micrograms was administered and MAC isoflurane was redetermined. Conscious rats (n = 35) were also examined for the presence of locomotor dysfunction following intrathecal administration of CP and SP. Animals were randomly assigned to each treatment group and the investigators were blinded.CP at 10 and 100 micrograms reduced MAC isoflurane by 9.9% and 15.3%, respectively (P < 0.05). Intrathecal administration of SP reversed the decreases in MAC by CP; however, locomotive activity was not changed.These results suggest that the NK-1 receptor plays an important role in determining the MAC of isoflurane by inhibition of pain transmission in the spinal cord.