The syndrome of cancer anorexia includes early satiety in man and a reduction in the duration of feeding in experimental animals. These aberrations suggest dysfunction of peripheral and/or central nervous system satiety mechanisms in tumor-bearing individuals. Since the gut peptide, cholecystokinin (CCK), has been implicated as a potent satiety cue in man and animals, plasma and brain concentrations of CCK were measured by radioimmunoassay in anorectic tumor-bearing rats. Plasma concentrations of immunoreactive CCK were not significantly altered in either an acute Walker 256 carcinosarcoma or more chronic methylcholanthrene-induced sarcoma animal model of cancer anorexia. However, levels of immunoreactive CCK were significantly reduced in the hypothalamus and cerebral cortex of animals bearing the methylcholanthrene sarcoma during both mild and severe anorexia. These data demonstrate that elevations in immunoreactive CCK are not a major factor in the etiology of cancer anorexia. If brain CCK is involved in satiety, tumor-bearing rats may be attempting to compensate for their anorexia by down-regulating CCK production.