Serotonin reuptake inhibitors (SSRIs) have today become the first-line treatment of premenstrual dysphoric disorder (PMDD). However, the actual success rate of these agents in clinical practice also depends on factors such as adequate dosing, duration of therapy and patient compliance. The aim of the current study was to investigate compliance and reasons for discontinuing tricyclic antidepressant (TCA) or SSRI treatment which had been prescribed for premenstrual syndrome. All women who were given an SSRI or TCA prescription for premenstrual symptoms at three gynecologic practices between January 1994 and December 1997 received a written questionnaire. In all, 202 women received the questionnaire, of whom 84.2% replied. Thirteen per cent never started TCA or SSRI treatment and 54% continued the therapy for more than 6 months. Reasons for discontinuing SSRI or TCA were negative side-effects (43%), other reasons (29%), a wish to deal with the problems 'naturally' (23%), fear of dependence (19%), not wanting to take these drugs (20%) and a desire to find out if the premenstrual symptoms had ended (18%). The main reason for poor compliance was negative side-effects, most often sexual dysfunction. The results of this study suggest that the future challenge in this area for gynecologists will be to ensure adequate education of patients and adequate monitoring of the initial phase of treatment.