The prophylactic effect of the tricyclic antidepressant doxepin given chronically in patients with mixed migrainous and tension headache, has been investigated in a double-blind cross-over trial. Twenty-three patients without serious medical, neurological or psychiatric diseases were included. They were given a course of 9 weeks of doxepin 100 mg daily and doxepin placebo each. Between the two courses a placebo period of 2 weeks was interposed. Only 14 patients completed the trial. The results showed no significant difference in number of headache days on doxepin in comparison to placebo, but on doxepin there was a significant reduction in terms of headache indices, and of the consumption of analgesics and ergotamine preparations. Ten of the 14 patients experienced side effects on doxepin (weight increase, drowsiness, dryness of the mouth).