The aim of our study is to evaluate the possible association between lower plasma cholesterol and depression in the elderly. 140 subjects over 65 years old of both sexes were enrolled, of which 60 were affected by depression (DSM-III-R and Hamilton test) and 80 composed a control group homogeneous for sex and age with the previous one. Plasma cholesterol, HLD-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglycerides were measured. A statistically significant difference between cholesterol and LDL-C (p < 0.001) was noted in the total group, in both males and females. Such modifications were independent of sex. In the group with lower cholesterol (cut-off < = 160 mg/dl) a prevalence of depression three times greater than subjects with higher cholesterol was found. In conclusion, the authors recommended a prudent use of lipid-lowering medications in the elderly because of its uncertain benefits.