The influence of a very low caloric diet (VLCD) on high density lipoproteins (HDL) is controversial. This study was designed to evaluate the influence of a VLCD on lipids and lipoproteins, especially on HDL subfractions (HDL2, HDL3) in obese women. After a 4-day period of isocaloric standard diet, 30 women at least 50% above ideal body weight were switched for 15 days on a protein-sparing modified diet providing 1.57 MJ per day. Mean body weight reduction was 5.6 ± 0.7 kg. After the VLCD, total, very low density lipoproteins (VLDL), low density lipoproteins (LDL) and HDL cholesterol significantly decreased in all the subjects (p < 0.01). Both HDL subfractions were depressed after the VLCD (p < 0.01) but the reduction occurred predominantly in the HDL2 subfraction, thus inducing a decrease in the HDL2 to HDL3 cholesterol ratio (p < 0.01). The VLCD was associated with a slight but not significant increase in the LDL to HDL cholesterol ratio. This increase was due mostly to the rise in the LDL to HDL2 cholesterol ratio (p < 0.01). Further studies are needed to evaluate the long-term changes of HDL subfractions during weight-reducing regimens