A group of moderately to severely depressed individuals with moderate anxiety were studied to determine the frequency and nature of pain complaints and their response to doxepin. It was discovered that 100% of these subjects had chronic pain complaints, most of which paralleled the course of depression. Headache was most commonly noted. Doxepin's analgesic effects were intimately associated with its antidepressant effects. There was a highly significant relationship between improvement of depression and reduction of pain on doxepin (P less than 0.005). Conversely, patients who obtained minimal antidepressant effect also obtained minimal analgesic effect. Psychophysiologic and biochemical hypotheses of this association of pain and depression are discussed.