The reliability of screening for high serum total cholesterol is adversely affected by the variability of cholesterol levels over time. This problem is investigated using data on repeated cholesterol measurements for 14,600 men and women in the MRC Mild Hypertension Trial. For measurements 1 year apart, the within-person coefficient of variation (CV) is 7%, which is substantial compared with the between-person CV of 15%. In a screening programme, this within-person variability may lead to the misclassification of individuals and inappropriate intervention. For example, 28% of middle-aged British men with a single cholesterol measurement above 6.9 mmol/l have a long-term average cholesterol below that value even without intervention. Using averages of several cholesterol measurements reduces, but does not eliminate, these problems. Furthermore, monitoring the effect of interventions in individuals by sequential cholesterol measurement may be unhelpful or even misleading. These problems cast serious doubt on the value of general population screening for high cholesterol levels.