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ABSTRACT: Lead (Pb) depresses growth in infants and young children. Our earlier studies using a weanling rat model of Pb exposure suggest that this Pb effect is due to depression of appetite. In the present study we examined whether this depression of appetite is consistent with a down-regulation of the appetite "set point" as described using dietary manipulations following either lesions of certain hypothalamic regions or 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. Two types of dietary manipulations were employed: (a) consumatory response to hyperalimentation (force-feeding), and (b) consumatory and growth response during the catch-up period following food restriction. In the hyperalimentation experiments, food intake was determined (a) with and without force-feeding, and (b) without Pb and with Pb administered either orally or systemically. Pb exposure reduced food consumption compared to controls. Force-feeding of a liquid diet further reduced food consumption, but only to the level that maintained total caloric intake at, or close to, the level of Pb animals not force-fed. In the food-restriction experiments, weanling rats had their food intake restricted for 4 days and then were provided free access to food, at which time one subgroup of these animals was exposed to Pb. Catch-up of previously food-restricted animals, in terms of food consumption and growth, was the same in the first 2 days, regardless of whether Pb was administered. During the next 10 days, the food intake and growth of the non-Pb-exposed, food-restricted animals gradually converged on the previously free-fed, non-Pb-exposed animals, whereas the food-restricted. Pb-exposed animals converged on the growth-depressed, previously free-fed Pb-exposed animals. All these responses to dietary manipulations are consistent with a reduced set point for appetite rather than with a nonspecific effect of Pb, e.g., aversion to food or general malaise.