Major phases of the physiology of food intake regulation remain hypothetical. There is a central regulatory mechanism for hunger and satiety, but the signals and messages that activate the brain centers remain conjectural. The alimentary tract regulation, the regulation by osmoreceptors, the thermostatic, the glucostatic, the lipostatic, the amino acid, and the hormonal food intake regulation theories leave many questions unanswered. Low molecular weight peptides appear to have an important effect on brain functions. Hypothalamic peptides such as thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin have been assigned new roles in various brain functions. The hypothalamus and probably other parts of the brain produce also anorexigenic peptides. Anorexia is a common manifestation of cancer. It is proposed that peptides, oligonucleotides, and other small metabolites produced by the cancer and by the tumor-bearing host are responsible for the genesis of the anorexia. They produce the anorexia through a peripheral effect on neuroendocrine cells and neuroreceptors and through a direct effect on hypothalamic and other central nervous system sensor and responder cells.