Interestingly, the success of bypass surgery may be as much hormonal as mechanical. Fasted rats with jejuno-intestinal bypass ate 32% less in the first hour of re-feeding than fasted rats given a sham procedure (Atkinson & Brent, 1982). When plasma from the bypass group following feeding was injected into a new group of fasting rats, the recipients ate 32% less in the first hour than rats injected from plasma from the sham bypass group. Thus it appeared that the reduction in appetite was hormonally driven. After intestinal resection in the rat, there is significant elevation in the concentration of PYY (Savage et al., 1985). With our current knowledge of the PYY 3–36 circuitry from the gut to the ARC of the hypothalamus, it is tempting to hypothesize that elevated circulating PYY 3–36 levels in patients with gastric or intestinal bypass contribute to a reduction in appetite and food intake. Gastric bypass surgery may also affect circulating ghrelin. Plasma ghrelin concentrations were recently measured in obese patients before and after diet-induced weight loss, and in patients who had previously undergone gastric bypass surgery. As predicted, circulating ghrelin increased with diet-induced weight loss. However, ghrelin levels were 77% lower in the gastric bypass group compared with matched BMI controls, and the usual premeal peaks were lost (Cummings et al., 2002). Under normal circumstances the presence of nutrients in the stomach is believed to suppress ghrelin secretion from the stomach. However, the observations of this study suggest that prolonged absence of nutrients or surgical manipulation of the stomach suppresses ghrelin secretion. Reduced circulating ghrelin with a possible elevation of circulating PYY 3–36 could account for the paradoxical decrease in hunger reported by most patients, and explain the long-term weight loss usually seen following gastric bypass surgery.