The effect of maternal hypercholesterolemia on the course of pregnancy and the development of offspring was investigated. Rats were fed either an enriched-cholesterol diet (HC) or a standard diet (control) from 1 week before mating until weaning of offspring. Compared with the control group, HC dams showed a fourfold increase in abortions, a twofold increase in neonatal mortality, smaller litter size, and lower birth weight of pups. At weaning, Na(+),K(+)-ATPase activity in the outer renal medulla was reduced in HC pups compared with control pups, suggesting retarded or impaired development of medullary nephron segments. At this point, to better examine the adverse effects of maternal hypercholesterolemia, the HC pups were divided into two groups: one fed a cholesterol-enriched diet (HC/hc) and the other a standard diet (HC/nc), while control pups were maintained on the standard diet. In adulthood, the HC/hc group showed growth impairment and reduced renal function, demonstrated by low creatinine clearance (0.24+/-0.04 ml/min per 100 g body weight) and high fractional excretion of sodium, potassium, and water ( P<0.05 vs. control). These effects were partially reversed in the HC/nc group. In this study, neither dams nor offspring developed hypertension. Thus, maternal hypercholesterolemia adversely affected pregnancy outcomes and the development of offspring by inducing abnormalities and thereby reducing renal function.