Previous studies of the prolactin response to D-fenfluramine in depressed patients have yielded inconsistent results. This may be because they did not address the question of suicidality. We carried out this study to test the hypothesis that lower prolactin response to D-fenfluramine is more closely associated with suicidal behavior than with depression itself. A D-fenfluramine test was performed in a sample of 18 healthy control subjects and in 85 drug-free inpatients with a DSM-III-R diagnosis of major depressive episode (49 with a history of suicide attempt, 36 without). Depressed inpatients with a history of suicide attempt showed a significantly lower prolactin response to D-fenfluramine compared to depressed inpatients without such a history and compared to control subjects. Healthy control subjects and depressed inpatients without a history of suicide attempt showed comparable levels of prolactin after D-fenfluramine. Time elapsed since suicide attempt did not influence prolactin level (baseline or post-stimulation). Results show that in our depressed drug-free inpatient sample, prolactin response to D-fenfluramine seems to be a marker of suicidality, but not of depression itself. We suggest that it is a trait marker of suicidality.