The sensitivity of SART-stressed (repeated cold-stressed) mice to substance P (SP) was studied. The behavioral responses to intrathecal SP in the stressed mice were less marked than those in non-stressed mice. The 50% effective dose of SP, however, did not differ between the 2 groups. Also, the antagonistic effect of intrathecal [D-Pro2, D-Trp7,9]-substance P against SP was not different. These results suggest that SART-stressed mice are subsensitive to exogenous SP and that the number but not the affinity of SP receptors may be altered.