The relationship between pupil size and subjective symptoms of opiate withdrawal during gradual opiate agonist detoxification has not yet been studied. In the current study, the authors sought to determine the relationship between pupil size and intensity of opiate withdrawal symptoms. To accomplish this, they examined 19 subjects meeting DSM-IV criteria for opiate dependence (304.00) on agonist therapy. All subjects were undergoing opiate detoxification with either methadone or the longer-acting 1-alpha acetylmethadol (LAMM). During two separate visits, subjects' pupil sizes were assessed in the dark using a pupillometer. At each visit, subjects completed two standardized assessment tools (the Subjective Opiate Withdrawal Scale [SOWS] and the Weak Opiate Withdrawal Scale [WOWS]) for measuring subjective symptoms of opiate withdrawal. It was found that changes in pupil size significantly correlated with WOWS, but not with SOWS, scores. Larger pupil sizes were associated with less withdrawal distress. The sensitivity of the pupillometric test to detect increases in opiate craving during opiate agonist medication reduction was 92%, with a specificity of 57%. The predictive value of a positive test was 79%, whereas the predictive value of a negative test was 80%. Pupillometry may provide an objective measure of the intensity of opiate withdrawal in subjects during gradual methadone detoxification.