We have previously demonstrated that the fetus with anencephaly is hypercholesterolemic. The plasma levels of total cholesterol and low-density lipoprotein cholesterol are threefold greater than those of normal fetuses. We have provided evidence that elevated low-density lipoprotein cholesterol levels were caused by reduced uptake and metabolism of low-density lipoprotein by atrophic adrenal glands deficient in low-density lipoprotein receptors. The purpose of the present investigation was to determine if other tissues, namely, skin fibroblasts, of the fetus with anencephaly were also deficient in low-density lipoprotein receptors. We compared the binding and metabolism of low-density lipoprotein by skin fibroblasts of fetuses with anencephaly and normal subjects. Cultures of skin fibroblasts were grown to confluency. Thereafter, the medium was changed to lipoprotein-deficient serum for 24 hours. The rate of uptake and degradation of iodine 125-iodo-LDL was determined as a function of time and concentration of low-density lipoprotein. The maximal specific binding of low-density lipoprotein was also determined. The rate of uptake, degradation, and the maximal binding of low-density lipoprotein was similar in skin fibroblasts of infants with anencephaly and normal subjects. We conclude that the elevated level of low-density lipoprotein cholesterol in cord blood of fetuses with anencephaly is not caused by deficiency of low-density lipoprotein receptors and metabolism in skin fibroblasts but instead by deficiency of low-density lipoprotein receptors and metabolism by atrophic adrenal glands.