The question of whether hypocholesterolemic treatment is associated with increased mortality due to suicide, violence and car accidents is controversial and of great importance. We investigated the effect of hypocholesterolemic dietary and drug therapy on dysphoric emotions. Twenty-five hypocholesterolemic men were started on a 3-month dietary modification plan; those who showed unsatisfactory cholesterol reduction were given, in addition, a hypocholesterolemic drug for up to 1 year. Lipid profile and change in dysphoric emotions were measured. During the whole period, a negative correlation was found between cholesterol level and depression. During the dietary period, a significant improvement in depression and guilt with no change in lipid profile was noted. Drug therapy significantly reduced cholesterol levels, with a trend toward increased depression (after 3 months) and a significant increase in aggression and guilt (after 1 year). We conclude that changes in dysphoric emotions occurring during hypocholesterolemic therapy cannot be completely explained by the changes in cholesterol levels.