The benefits of physical activity in reducing cardiovascular disease (CVD) are thought to be mediated through changes in blood lipids, insulin sensitivity, and thrombogenic factors. Few studies have addressed the effects of both long-term physical activity and inactivity on these factors. The authors assessed associations between long-term leisure-time physical activity, television watching, and biomarkers of CVD risk among 468 healthy male health professionals. Prior to blood collection in 1993-1994, physical activity and television watching were assessed biennially from 1986 to 1994 by a questionnaire. Physical activity was expressed as metabolic equivalents-hours per week. Multivariate linear regression analyses showed that metabolic equivalents-hours in 1994 were significantly associated with high density lipoprotein cholesterol (HDL cholesterol) (positively) and with leptin and C-peptide (inversely). The average number of hours of television watching assessed in 1994 was significantly positively associated with low density lipoprotein cholesterol and significantly inversely associated with HDL cholesterol and apolipoprotein A1. Average hours of television watching per week assessed in 1988-1994 was positively associated with leptin levels (p < 0.01). The associations of television watching and vigorous activity with leptin and HDL cholesterol were independent of each other. In conclusion, physical activity and television watching were significantly associated with several biochemical markers of obesity and CVD risk.