Sexual dysfunction is commonly encountered in patients treated with antidepressants. The exact mechanism responsible for the sexual impairment is as yet unclear, although activation of the serotonergic system has been implicated, In the present study, we examined the effect of the 5-HT2a/2c and alpha(2) antagonist mianserin in the treatment of patients with sexual dysfunction induced by serotonin reuptake inhibitors (SRIs), Mianserin 15 mg was coadministered to 15 male subjects with new-onset sexual dysfunction who were under treatment with SRIs. Four major domains of sexual activity-desire, erection, orgasm, and satisfaction-were assessed once weekly for 4 weeks. At the end of the study, 9 of the 15 subjects reported a marked improvement in their sexual functioning, 2 reported partial improvement, and only 4 subjects showed no improvement at all. The beneficial effects were prominent in the areas of orgasm and satisfaction and were usually noted within the first and second week of mianserin treatment. The addition of mianserin to the treatment regimen was not associated with either improvement or worsening of the basic psychiatric clinical status.