Sixteen patients with a headache resembling the so-called "tension headache" and a clear response to doxepin (demonstrated in a previous work) were given femoxetine, 400 mg p.d., and placebo in a cross-over, double-blind fashion. Only single blindness was kept in the last third of the study. Placebo and femoxetine tablets were each given for four weeks. Whereas there was a daily or practically daily occurring headache untreated, placebo was associated with a headache frequency of 92%. The corresponding figures for doxepin and femoxetine were 27% and 41%, respectively. Femoxetine led to transitory nausea and gastrointestinal discomfort, but in contrast to doxepin, no weight gain and only slight, if any, sedation. Most patients preferred femoxetine to doxepin. Femoxetine, an antidepressant phenylpiperidine derivative with predominant serotonin re-uptake inhibition (little effect on noradrenaline), thus seems to counteract so-called "tension headache".