There are contradictory results regarding the pattern of seasonal variation of serum lipids. The aim of this study was to compare serum lipid levels in different seasons in participants of the Tehran Lipid and Glucose Study. This was a cross-sectional study among 2890 men and 4004 women 20-64 years old from the participants of Tehran Lipid and Glucose Study (TLGS) between 1999 and 2001. Mean values of serum lipids in different seasons were compared with Analysis of Covariance (ANCOVA) after adjustment for age, physical activity level, smoking, BMI and Waist-to-hip ratio. In men, there was a significant trend for change in the values of cholesterol, LDL-C and HDL-C in different seasons, with higher cholesterol and LDL-C values in winter than in summer (P < 0.05). In women, only the mean values of triglycerides were significantly different between different seasons with values lower in winter than in summer. There was a 26.2% relative increase in the prevalence of hypercholesterolemia (> or = 240 mg/dl) in winter than in summer in men. The corresponding increase in the prevalence of high LDL-C (> or = 160 mg/dl) was 26.7% and 24.9% in men and women, respectively (P < 0.05). The prevalence of high triglycerides (> or = _ 200mg/dl) in women significantly decreased (23.8%) in winter relative to summer (P < 0.001). This study showed that there is seasonal variability in serum lipid values and this variability is greater in men than women. The increase in the prevalence of high LDL in winter in both sexes must be considered in population screening and in the follow-up of hyperlipidemic patients.