Opioid-GABAergic interactions for the treatment of post-operative pain were investigated in two double-blind, placebo-controlled experiments. We first studied the effect of pre-operatively administered baclofen, a GABAB receptor agonist, on the analgesia produced by intravenously administered morphine, a predominantly mu-opioid analgesic. In a separate trial, we studied the effect of baclofen on the analgesia produced by pentazocine, a predominantly kappa-opioid analgesic. While baclofen alone did not affect the level of post-operative pain, morphine analgesia was significantly enhanced by baclofen compared to placebo. In contrast, baclofen did not affect the level of pentazocine analgesia: however, females receiving pentazocine showed significantly greater analgesia than males.