OBJECTIVE: The aim of this study was to investigate associations between plasma apoM concentration and HDL apoA-I and apoA-II kinetics in 60 overweight-obese, insulin resistant men. METHODS: Plasma apoM concentration was determined using a sandwich ELISA with two monoclonal antibodies (CV<5%). The kinetics of HDL apoA-I and apoA-II were measured using intravenous administration of D(3)-leucine, gas chromatography-mass spectrometry and multi-compartmental modeling. RESULTS: Plasma apoM was inversely associated with body mass index and positively associated with plasma total cholesterol, LDL cholesterol and HDL cholesterol (p<0.05). There were no associations between plasma apoM and plasma triglyceride, NEFA, insulin, glucose, HOMA score or adiponectin concentrations. Plasma apoM was positively associated with both apoA-I and apoA-II concentrations (r=0.406, p<0.01 and r=0.510, p<0.01, respectively) and negatively associated with HDL apoA-I and apoA-II fractional catabolic rate (FCR) (r=-0.291, p=0.03 and r=-0.291, p=0.026, respectively). No significant associations were observed between plasma apoM and HDL apoA-I and apoA-II production rate. In multivariate regression models, both plasma apoM and triglycerides were significant, independent predictors of HDL apoA-I FCR (adjusted R(2)=16%, p<0.01) and HDL apoA-II FCR (adjusted R(2)=14%, p<0.01). CONCLUSION: ApoM may be a significant, independent predictor of HDL apoA-I and apoA-II catabolism in overweight-obese, insulin resistant men.