This work was undertaken to determine the comparative effects of metformin and phenformin on the development and the regression of atherosclerosis in cholesterol fed rabbits: 1. Both compounds reduced very significantly the elevated lipid content of plasma induced by a high cholesterol diet, they limited and sometimes suppressed the appearance of lipid deposits in the liver. Only metformin prevented the development of aortic and coronary lesions. 2. In rabbits fed a cholesterol enriched diet for a period of 2 months, followed by a normal diet during 12 months, both compounds accelerated the sponanteous regression of hyperlipidemia and of the excess lipids in the liver, observed in the corresponding controls. Only metformin promoted a marked elimination of arterial lipids and displayed a protective action against coronary atherosclerosis.