During the past 20 years, there has been described a group of profoundly anxious and phobic patients, who are not amenable to psychological forms of treatment or to the major and the minor tranquilizers, but who respond dramatically to tricyclic and MAO inhibitor medication. The separation of this drug-responsive syndrome from other anxiety disorders constitutes a major advance in psychiatry. This paper discusses the implications of these findings for the treatment of psychosexual disorders. To illustrate the hypotheses and discussion, the case histories of three patients with sexual phobias are described. All had been treatment failures with sex therapy and psychotherapy but responded to a combination of tricyclic medication and sex therapy which was modified to accommodate the special needs of sexually phobic patients.