Homocysteine levels have been reported to be elevated in psychiatric patients. We investigated the homocysteine levels in bipolar patients, their first-degree relatives and normal healthy controls. The study comprised of two hundred seven patients with bipolar affective disorder, two hundred ninety-eight relatives of patients and three hundred forty normal subjects. Homocysteine level was found significantly higher in patients and their relatives compared to controls. We also found significant negative correlation between homocysteine and HDL-cholesterol in patients with bipolar affective disorder. In conclusion, increased homocysteine levels might result from low HDL-cholesterol and high triglyceride and cholesterol that cause oxidative stress that is more pronounced in psychiatric disorders. Subjects who have elevated homocysteine might be sensitive to develope bipolar disorders compared to healthy subjects.