Apolipoprotein M (apoM), a 25 kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with HDL. Studies in mice have suggested apoM to be important for the formation of pre-beta-HDL and to increase cholesterol efflux from macrophage foam cells. Overexpression of human apoM in LDL receptor-deficient mice reduced the atherogenic effect of a cholesterol-rich diet. The aim of the present study was to investigate whether the apoM levels in man predict the risk for coronary heart disease (CHD). ApoM was measured in samples from two separate case-control studies. FINRISK '92 consisted of 255 individuals, of whom 80 developed CHD during follow-up and 175 were controls. The Copenhagen City Heart Study included 1,865 individuals, of whom 921 developed CHD during follow-up and 944 were controls. Correlation studies of apoM concentration with several analytes showed a marked positive correlation with HDL and total cholesterol as well as with apoA-I and apoB. There was no significant difference in mean apoM level between CHD and control subjects in either study. In conditional logistic regression analyses, apoM was not a predictor of CHD events, [odds ratio (95% CI) 0.97 (0.74-1.27) and 0.92 (0.84-1.02), respectively]. In conclusion, no association between apoM and CHD could be found in this study.