Low plasma concentrations of active transforming growth factor β (TGF-β) are associated with coronary artery disease although the mechanism causing decreased active TGF-β is uncertain. Plasmin activates TGF-β and therefore increased plasminogen activator inhibitor-1 (PAI-1) may cause decreased active TGF-β concentrations. TGF-β is a hydrophobic protein and we hypothesized that post-prandial lipemia would be associated with a decrease in active TGF-β concentrations. To test this hypothesis we studied the response of lipoproteins, PAI-1 and TGF-β in individuals who completed a fat tolerance test. After 8 hours there was a 42% mean reduction in plasma active TGF-β concentrations (p<0.0001). PAI-1 levels increased from 6.8±5.5 to 10.6±5.5ng/ml (p<0.0001) and the increase in PAI-1 levels over 8h was correlated with the decrease in active TGF-β concentrations during the test (r=-0.55, p<0.0001). The results suggest that post-prandial lipemia is linked to potentially atherogenic changes in PAI-1 and active TGF-β concentrations and 2.) the decrease in TGF-β levels is mediated in part by the increase in PAI-1 concentrations.