Imprinting of an increased sensitivity to a high-fat, high cholesterol (HFHC) diet by dietary manipulation in early life was studied in two strains of rat, i.e. in Prague hereditary hypercholesterolaemic rats (PHHC) and Wistar rats, from which the PHHC strain was obtained by selection and inbreeding. Whereas no effect of early life nutrition on cholesterolaemia induced by HFHC diet was found in control Wistar rats, significant imprinting of increased sensitivity to the same diet was demonstrated in PHHC rats. This imprinting increased the concentration of apoB- containing lipoprotein and liver cholesterol concentration in animals fed HFHC diet for a period of two months after weaning. No effect of this imprinting on endogenous cholesterol synthesis could be demonstrated. It is concluded that imprinting of increased sensitivity to HFHC diet by dietary manipulation in early life is not a general phenomenon but depends on underlying genetic predisposition(s).