The lipoprotein profile, the HDL subfractions and the apolipoprotein (apo) A-I conformation of HDL were determined in 119 patients with myocardial infarction and 119 controls, paired for age. Apo A-I conformation was assessed by its immunoreactivity towards two monoclonal antibodies, 5F6 and 3G10. HDL phospholipid levels and fatty acid composition were also determined. HDL and HDL3 cholesterol, apo A-I, LpA-I and LpA-I:A-II levels were significantly lower in patients than in controls, whereas the levels of total and LDL-cholesterol and of apo B were not different. Apo A-I immunoreactivity against MAb 5F6 was significantly better in patients than in controls, while the immunoreactivity against 3G10 was similar. Paired stepwise logistic regression showed only apo A-I, HDL3 cholesterol and 5F6 immunoreactivity to be significantly related to myocardial infarction. After adjustment for HDL cholesterol, lower levels of HDL phospholipids and polyunsaturated fatty acids (PUFA) were found in patients compared with controls. Hence, of all HDL markers, apo A-I and HDL3 cholesterol appear to be the most informative. Also, lower HDL phospholipid and PUFA content may explain a different apo A-I conformation in patients with myocardial infarction.