The relationships between subcutaneous abdominal and femoral fat cell lipolyses, plasma free-fatty acid (FFA) levels and metabolic variables considered as risk factors for cardiovascular disease (CVD) (plasma glucose, insulin and lipoprotein levels) were investigated in 54 men, aged 36 +/- 3 (SD) years, covering a wide range of body fatness values (body mass indices from 19 to 34 kg m-2). Although there were no consistent relationships between femoral fat cell weight and the metabolic profile, positive and significant associations were found between abdominal fat cell weight and most of the metabolic indices. However, abdominal fat cell lipolysis measured with an alpha 2-(clonidine) or a beta-agonist (isoproterenol) was unrelated to metabolic variables. In contrast, femoral fat cell lipolysis measured in the presence of clonidine was positively associated with fasting plasma insulin, cholesterol (CHOL) and apolipoprotein (apo) B levels, as well as with LDL-CHOL and LDL-apo B concentrations. No association was found between isoproterenol-stimulated lipolysis of femoral adipocytes and the metabolic profile. Comparison of two subgroups of men with either low or high femoral residual lipolysis with clonidine revealed that subjects with the lowest femoral alpha 2-adrenergic component (i.e. the highest residual lipolysis) displayed significant alterations in both plasma lipid-lipoprotein and glucose-insulin levels which could be predictive of an increased risk of CVD. Free fatty acid (FFA) levels measured in the fasting state and during an oral glucose tolerance test (OGTT) were positively associated with fasting plasma insulin and triglyceride levels as well as with both glucose and insulin areas measured during the OGTT. However, regional adipose tissue lipolysis measured in vitro was unrelated to plasma FFA levels. These results support the view that both femoral adipose tissue lipolysis and plasma FFA levels are significant correlates of plasma glucose-insulin homeostasis and lipoprotein-lipid levels, in men. However, as adipose tissue lipolysis and plasma FFA are unrelated to each other, they may be associated with risk variables through independent mechanisms.