In a number of previous reports, an association of altered, in most cases lower, serum cholesterol levels with depression, suicidal ideation and current or past suicidal behavior has been suggested. In this investigation, the course of serum cholesterol concentrations was measured in depressed patients during treatment. Ninety-two inpatients with a major depressive episode were included. Serum lipid concentrations were assessed at admission, after 1 week and after 4 weeks of antidepressant treatment. Degrees of depression and suicidality were measured with the Hamilton Depression Rating Scale. Although there was a significant reduction in depression and suicidality scores, neither a significant change in serum cholesterol levels nor a correlation between cholesterol levels and clinical improvement was found. Further, there were no significant differences in lipid levels between patients with and without a history of attempted suicide. In patients who had used a violent method, there was a trend for lower total cholesterol levels compared to those who had poisoned themselves. The results of this study do not support the hypothesis of an association of serum cholesterol with the course of depression and suicidal ideation. Cholesterol levels do not appear to be an appropriate biological marker for suicidality during the first 4 weeks of treatment in patients with a major depressive episode.