Background: High density lipoprotein (HDL) cholesterol is inversely associated to atherosclerotic cardiovascular risk. Disturbances in HDL cholesterol plasma leves are frecuent in the Chilean population, however the pathophysiological mechanisms are unknown. Aim: To evaluate the mechanisms involved in the hypo and hyper alfalipoproteinemias in Chilean subjects. Materials and Methods: Twenty three subjects with hyperalphalipoproteinemia and 12 with hypoalphalipoproteinemia, paired with control subjects (col-HDL between 35 and 55 mg/dl) were studied. We measured plasma lipids, subfractions and sizing of HDL particles and enzymatic activity of cholesteryl ester transfer protein (CETP), lecithin: cholesterol acyltransferase (LCAT), lipoprotein lipase (LPL) and hepatic lipase (LH). Results: Subjects with hyperalphalipoproteinemia showed significantly higher levels of total HDL-cholesterol (70±2 vs 44±1 mg/dl), HDL 2 (30±3 vs 5±1 mg/dl), Apo A I (175±3 vs 146±4 mg/dl), lower HL activity (23,7±0,8 vs 32,4±1,8 mmol/h/l) and HDL particles of greater size, compared to their controls. Subjects with hypoalphalipoproteinemia, showed significantly lower levels of total HDL-cholesterol (26±1 vs 48±2 mg/dl), HDL 3 (21±1 vs 40±2 mg/dl), Apo A I (107±5 vs 145±7 mg/dl), lower LCAT activity (18,6±1,9 vs 26,2±1,6 nmol/h/ml) and smaller HDL particles, compared to their controls. Conclusion: Changes in hepatic lipase and lecithin cholesterol acyltransferase activities may explain the hyper and hypo alphalipoproteinemia respectively, in Chilean subjects (Rev Méd Chile 2004; 132: 421-8)