BACKGROUND This study aimed to investigate to what extent cholesterol levels change in individuals in different age groups over an 18-year period. Factors that contribute to the changes, with respect to prevention of cardiovascular disease, were taken into account. METHODS In 1977 serum cholesterol, systolic and diastolic blood pressures, body mass index, and smoking habits were measured in a cohort of 7,092 patients (men and women from 20 to 50 years of age) from six general practices in The Netherlands. In 1995, a sample of 2,600 of these same patients were invited to take part in a similar screening program; 2,335 patients, consisting of 1,171 men and 1,164 women, agreed to participate. Patients were derived from both high-risk and low- to normal-risk category in 1977. The differences in cholesterol between 1977 and 1995 were calculated and cholesterol levels were tracked over the study period by determining Pearson correlation coefficients. A multiple linear regression analysis was performed to investigate the determinants influencing the changes in cholesterol level. RESULTS The mean cholesterol levels rose during the study period in all age groups. The highest mean increase in men was 1.23 mmol/L, or 20%, in the youngest age group (20-24 years), and in women the maximum mean increase was 1.12 mmol/L, or 17%, in the age group 40-44 years. Correlation coefficients between the 1977 and 1995 readings varied from 0.63 in the youngest age group to 0.41 in the oldest. Body weight change during the study period, more than initial body weight, was found to have influenced the rise in serum cholesterol. At basic screening, 19.2% of the men and 12.4% of the women had cholesterol levels of 6. 5 mmol/L or higher, as against 35.8 and 36.8%, respectively, in 1995. CONCLUSIONS Over an 18-year period cholesterol level increased in most subjects, at a younger age in men than in women. The highest increase in women took place during the menopausal period. Weight gain, more than baseline weight, had a positive influence on the increase in cholesterol.