Serum cholesterol levels were determined in 1011 male participants of the Baltimore Longitudinal Study of Aging. This study presents the longitudinal changes in serum cholesterol from 1 July 1963 to 30 June 1977. Serum cholesterol values dropped 6% between 1970 and 1972. The span of this study was divided into two eras, one preceding and one following the drop. The effects of obesity, selected dietary constituents and physical activity were examined in an attempt to explain the secular change in serum cholesterol. Serum cholesterol levels were not significantly correlated to levels of weight or body mass index. Changes in weight were significantly positively correlated with changes in serum cholesterol. Overall, however, the study population did not experience a significant drop in weight and therefore, this relationship could not explain the observed drop in serum cholesterol. There were virtually no significant correlations between the absolute value of any of the dietary variables examined and the absolute level of serum cholesterol. There were significant but small changes in most dietary constituents; however, only changes in caloric intake were significantly positively correlated with changes in serum cholesterol. Because the overall change in caloric intake was small, it could explain less than 1 mg/dl of the 11 mg/dl drop. There was no overall change in physical activity. No significant correlations were found between either the level or change in physical activity and the level or change in serum cholesterol. It is concluded that neither weight nor physical activity could account for the observed changes in serum cholesterol. Changes in dietary constituents were significant and in a direction which would predict a lower serum cholesterol. However, for the group, dietary changes could not fully explain the drop in serum cholesterol. For individuals, the changes in diet poorly predicted changes in serum cholesterol. It is suggested that the observed secular drop in serum cholesterol may be due to factor(s) other than those studied.