The aim of this study was to examine the effect of i.v. methadone on the plasma arginine-vasopressin (AVP) levels and urine production in 9 conscious dogs. A highly significant increase from the baseline plasma AVP values of below 3 pg/ml occurred within 5 min following methadone administration. Maximum levels were reached within 30-50 min post-injection and varied from 18.5 to 100 pg/ml. A significant decrease in urine production was not seen under these experimental conditions. Mean arterial blood pressure did not change significantly during the experiment. Apart from the partial influence of the methadone-induced respiratory acidosis, we postulate a direct relationship between i.v. administration of methadone and the increased plasma AVP levels in dogs.