The associations of adipose tissue lipoprotien lipase (AT-LPL) activity with body fatness and plasma lipoprotein levels were studied in the light of the recently described regional differences in AT-LPL activity. In this regard, heparin-releasable LPL activity was measured in abdominal and femoral adipose tissues of 29 pre-menopausal women. Body fatness variables were all positively correlated with abdominal and femoral AT-LPL activities expressed per 10(6) cells. However, abdominal and femoral AT-LPL activities expressed per unit of cell surface displayed divergent association patterns with body fatness and plasma lipoprotein levels. Indeed, only abdominal AT-LPL activity remained significantly correlated with body fatness variables after adjustment for fat cell surface. Furthermore, whereas abdominal AT-LPL activity tended to be negatively correlated with plasma HDL-cholesterol levels, femoral AT-LPL activity was positively correlated with plasma HDL2-cholesterol (r = 0.40, P less than 0.05) concentration and with the HDL2-cholesterol/HDL3-cholesterol ratio (r = 0.49, P less than 0.01). These results demonstrate the importance of taking into account the regional variation in metabolic activity of adipose tissue when studying its associations with body fatness, and with plasma lipoprotein levels. The lack of association between abdominal AT-LPL activity and plasma HDL2-cholesterol levels lead us to suggest that AT-LPL activity may not be causally related with plasma HDL levels.