Leptin deficiency has been associated with extreme obesity and hyperphagia in rodents and humans. A rare genetic disorder in humans yields the absence of the hormone leptin, extreme obesity, and a ravenous appetite. Reports on these rare cases have indicated that therapy using leptin injections can yield significant weight loss and changes in appetite. The aim of this report on acute leptin therapy in three leptin deficient adults was to provide a microanalysis of changes in eating behavior and ratings of hunger and satiety. In addition to substantial weight loss, 15 weeks of leptin therapy was associated with approximately 50% reduction in food intake and substantial changes in ratings of hunger and satiety before most meals. After short-term leptin therapy, the three participants ate until ratings indicated they were satiated, which was comparable to the ratings before leptin therapy. These findings suggest that one of the primary effects of acute leptin therapy may be to reduce the ravenous hunger associated with leptin deficiency, resulting in reduced food intake and significant weight loss. These results are discussed in the context of the scientific literature pertaining to leptin and its effects on appetite and obesity.