The effects of acute and chronic desmethylimipramine (DMI) administration on 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in plasma and urine were examined in eight depressed inpatients. DMI treatment induced an immediate and continuous highly significant reduction in plasma MHPG throughout the 30-day treatment period. This effect was not related to treatment response. In contrast to plasma MHPG, there was no uniform effect of DMI treatment on urinary MHPG. Chronic DMI treatment increased or did not change urinary MHPG in the three treatment responders and decreased urinary MHPG in five nonresponders. The correlation between plasma and urinary MHPG during the placebo period was not significant, and the effect of DMI treatment on the two measures differed markedly.