Early exposure to cholesterol-enriched, high fat diets has been reported to affect serum cholesterol levels in adult rats. In this study, we investigated the role of dietary fat alone, without cholesterol, by feeding to pregnant rats (from day 18 of gestation) experimental diets containing either high fat (corn oil), low sucrose (HF) or low fat, high sucrose (HS). After birth, mothers and pups were fed the diets until weaning (30 days), when serum cholesterol levels were the same in both groups of pups. Animals were fed stock diet until 7 months. At that time, half the animals from each original group (HF or HS) were challenged with HF diet for 3 days; the other half were fed stock diet. There was no significant difference in serum cholesterol between HF and HS animals fed stock diet: HF, 73 +/- 7 mg/dl (n = 11); HS, 80 +/- 19 (6); P greater than 0.25. Animals originally fed HF diet significantly raised serum cholesterol in response to late HF challenge (140 +/- 31 mg/dl, n = 10, P less than 0.001 vs. stock fed); the original HS-fed group did not (93 +/- 7 mg/dl, n = 5, P greater than 0.19). Early exposure to HF diet, even without cholesterol, could evoke a hypercholesterolemic response in adulthood following challenge by brief exposure to HF diet.