In Syrian hamsters, reproduction is sensitive to the availability of metabolic fuels. Estrous cycles can be interrupted by brief periods of food deprivation, by pharmacological inhibition of glycolysis and fatty acid oxidation, or by increasing energy demands for thermoregulation. We predicted that manipulations that divert an excessive portion of the metabolic fuel supply into storage also should inhibit reproduction. Redirection of metabolic fuels from oxidation to storage was accomplished by treatment with protamine zinc insulin suspension (PZI). Syrian hamsters treated with PZI and fed ad libitum increased their food intake by approximately equal to 40% and body fat stores, but there was no effect on estrous cycles. When PZI-treated hamsters were limited to approximately equal to 110% of their preinjection food intake, they still fattened, and there was a significant inhibition of estrous cyclicity. Thus, in the absence of overeating, PZI-enhanced energy storage may lead to a shortage of oxidizable metabolic fuels with the result that reproduction is inhibited in favor of processes essential for survival (e.g., cellular maintenance, thermoregulation). It is unlikely that insulin-induced anestrus is due to actions of PZI unrelated to metabolic fuel partitioning, because the hormone had no effects on estrous cyclicity in ad libitum-fed hamsters. These findings are inconsistent with the hypothesis that nutritional infertility is due to the failure to maintain a minimum body fat content and raise the possibility that the infertility associated with some types of obesity could be due in part to a disorder of macronutrient partitioning.