We studied some life-style characteristics that may predict changes in total serum cholesterol and cholesterol bound to high density lipoproteins (HDL-cholesterol) in a sample of 980 healthy Spanish employees of both sexes who were followed for three years. All workers participated in a multifactorial program aimed at preventing cardiovascular disease. Linear regression models were fitted with changes in total and HDL-cholesterol as the dependent variables, after eliminating variability due to the influence of basal values. The association between lifestyle factors and lipid changes was controlled for dietary modifications. In the multivariate analysis, decreases in body mass index, and in alcohol consumption were associated with significant reductions in total serum cholesterol. Maintaining sports at post-test or starting to practice them in the interim was also significantly and independently associated with favourable changes in serum cholesterol. Leisure-time exercise (p = 0.002) and giving up smoking (p = 0.06) were each associated with increased HDL-cholesterol.