Alcohol dependence is often comorbid with depression. The purpose of the present study was to compare serum brain-derived neurotrophic factor (BDNF) levels between depressive patients with and without alcohol dependence. Our subjects were 16 inpatients (M/F: 13/3, age: 48 +/- 8 years) at our university hospital who met the DSM-IV-TR criteria for both major depressive disorder and alcohol dependence and whose Hamilton Rating Scale for Depression (HAM-D) scores were at least 15. Twenty sex- and age-matched depressive patients and 20 healthy subjects were also examined. Serum BDNF levels in the depressive patients with (9.0 +/- 4.3 ng/ml) and without (9.8 +/- 5.2 ng/ml) alcohol dependence were significantly lower than those in the healthy subjects (21.1 +/- 7.0 ng/ml); however, no significant difference was found in the serum BDNF levels of depressive patients with and without alcohol dependence. Eight of the 16 (50%) depressive patients suffering from both depression and alcohol dependence responded to 8 weeks of treatment with antidepressant drugs which significantly increased their serum BDNF levels. These results suggest that the serum BDNF level is a useful biological marker for depression in patients with alcohol dependence.