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Introduction: Lithium has been found to be very effective in prophylactic treatment of affective disorders. However, approximately one-third of patients do not respond to this treatment, which does not become apparent until after a year or more of treatment. Therefore, predictors are needed to avoid a long and unsuccessful therapy with risk of severe side effects. Since lithium acts as a serotonin agonist in prophylactic treatment, a predictor of being able to identify patients with low serotonergic activity, who may be responders to lithium, is promising. To determine whether the loudness dependence (LDAEP) of primary, but not of secondary, auditory-cortex-evoked activity, which is inversely related to central serotonergic neurotransmission, could be such a predictor, responders and non-responders to prophylactic lithium treatment were compared. Methods: Thirty patients with uni- and bipolar affective disorders, who have taken a prophylactic lithium medication continuously for at least 3 years, were included in the study. Patients were classified as responders if they had no hospitalization within the past 3 years. Dipole source analysis allowing us to separate evoked activity of the primary and secondary auditory cortex was used. Results: The LDAEP of the primary, but not of the secondary, auditory cortex was significantly stronger in the responders to the lithium treatment than in the non-responders, implicating low serotonergic function in these patients. Discussion: This finding, which is in line with previous studies, suggests that loudness dependence of primary auditory-cortex-evoked activity could be a clinically relevant predictor of prophylactic treatment with lithium in affective disorders.