Seasonal variations were observed for fasting total plasma cholesterol, high-density lipoprotein-cholesterol (HDL-C), estimated low-density lipoprotein-cholesterol (LDL-C), and the ratio of HDL-C to total cholesterol (TC), measured in 5,244 middle-aged men and women in Jerusalem. HDL-C was highest in winter and lowest in summer, and triglycerides showed a mirror image of this pattern. TC and LDL-C followed a more complex wave form, levels of these being high in the winter, decreasing to a trough in the summer and increasing rapidly to a peak in the autumn. The ratio of HDL-C to TC was lowest in early autumn and highest in winter and early spring. There were two- to fivefold changes in the prevalence of hypercholesterolemia, hypertriglyceridemia and high LDL-C according to the season of examination. These findings imply that clinicians should take season into account when diagnosing hyperlipidemia and when evaluating apparent success or failure in its treatment. Studies of lipid distributions and of interventions aimed at lipid modification need to consider the potentially confounding effects of season.