Administration of human chorionic gonadotropin (hCG) to pregnant mare's serum gonadotropin – hCG primed rats results in the loss ofin vitroresponsiveness of the ovaries to exogenous gonadotropins for progesterone production. This state is associated with a loss of membrane receptors for hCG and a concomitant increase in lipoprotein receptors. Although lipoproteins potentiated gonadotropin response in ovaries from saline-injected rats, no stimulation was observed in hCG-desensitized ovarian cells. Examination of the time course for the loss of lipoprotein response after hCG injection revealed that injection with 50 IU of hCG results in a loss of gonadotropin response as early as 1 h after injection, but exogenous cholesterol-carrying lipoprotein fractions, LDL and HDL, were capable of stimulating progesterone production up to 4 h after hormone injection. Measurement of endogenous cholesteryl ester content showed that there was a 72% decline during this period with a concomitant increase in the basal progesterone production. One hour after hCG injection there was no stimulation of steroidogenesis by hCG in the presence or absence of exogenous lipoproteins. The refractoriness to exogenous hCG appeared only 4 h later when the hCG dose was reduced to 10 IU, whereas with 25 IU of hCG, the effect was similar to that observed using 50 IU of hCG. Such diverse steroidogenic stimuli as hCG, LH, LDL, cAMP, and cholera enterotoxin failed to stimulate progesterone synthesisin vitroin luteal cells of rats injected with 50 IU of hCG 48 h prior to sacrifice. Cellular uptake of reconstituted LDL bearing [3H]cholesterol linoleate was increased twofold in hCG-desensitized rat ovarian cells, whereas incorporation of [3H]cholesterol into progesterone from this reconstituted LDL was not stimulated by exogenous hCG. Examination of the binding of [125I]iodoLDL and [125I]iodoHDL to isolated plasma membrane from luteal cells showed that the binding of both these lipoproteins was increased twofold within 12 h after hCG injection, but returned to control levels by 72 h. From these results it is concluded that during hCG-induced loss of progesterone production in the ovary, the cells are fully capable of binding and transporting exogenously supplied plasma lipoprotein tractions. The steroidogenic lesion arises from the loss of hCG receptor mediated responsive system, but is not related to loss of the substrate pool needed for steroidogenesis.