Progesterone synthesis by the human corpus luteum requires a source of cholesterol, which can be derived from both local synthesis and uptake of low density lipoproteins (LDL). When the corpus luteum is maintained in organ culture, progesterone synthesis is primarily dependent on LDL and the rate of progesterone production during growth in a LDL-free media is suboptimal. An in vivo situation analogous to that of corpus luteum grown in LDL-depleted media exists naturally in patients with abetalipoproteinemia. To determine whether a complete deficiency of plasma LDL affects serum concentrations of progesterone (particularly during the luteal phase) or those of other hormones, we have measured the serum concentrations of luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol, estrone, and progesterone during the menstrual cycle in a patient with phenotypic abetalipoproteinemia (on the basis of homozygous hypobetalipoproteinemia). Our results show a normal cyclical pattern with midcycle increases in the concentrations of luteinizing and follicle-stimulating hormones, prolactin, and estrogens but a distinctly subnormal increase in the luteal phase concentrations of progesterone. These results suggest that, in patients with phenotypic abetalipoproteinemia, the absence of LDL leads to an impairment in the maximal rates of production of progesterone by the corpus luteum.