Two groups, each with ยฎve healthy male volunteers, received pairings of a distinct environment, the laboratory, with administrations of the muscle relaxant carisoprodol (CSP group), or pairings of the same environment with administrations of an inactive agent (control group). The control group received carisoprodol at home. This procedure was in eect in three sessions, each spaced 1 week apart. The CSP group received an inactive agent in the fourth session, and the control group received carisoprodol. The administration procedure was hypothesized to constitute a conditioned stimulus (CS) in the CSP group. The results showed that carisoprodol decreased blink reยฏex amplitude and duration. However, increased blink reยฏex amplitude was seen in the CSP group when the inactive agent was administered, which is opposite to the eect of carisoprodol. This indicates that a drug-antagonistic conditioned response was elicited by the CS in the CSP group. Moreover, blink reยฏex amplitude was increased in the CSP group compared to the control group when carisoprodol was administered, indicating that the antagonistic conditioned response decreased the eect of carisoprodol. The results suggest a role for antagonistic conditioned responses in human drug tolerance.