Stability of body composition requires that energy intake equals energ
y expenditure when integrated over prolonged periods. As recent human
studies have failed to demonstrate active changes in energy expenditur
e with changes in body composition, it is likely that energy intake is
continually adjusted to preserve a constant total adipose tissue mass
. If adipose tissue mass is regulated directly, then there must be som
e input reflecting this quantity to the central nervous system for the
purpose of making corrective changes in appetite when total body fat
content fluctuates. The nature of this input has been examined in a va
riety of animal experiments involving induced weight change, lipectomy
, plasma transfer from obese or satiated animals to hungry animals, an
d parabiosis between obese and lean animals. The bulk of evidence sugg
ests that the plasma level of one or more currently unidentified stabl
e circulating molecules increases in proportion to total body fat cont
ent and augments the effect of meal-related satiety signals in the cen
tral nervous system. The implications of this adipose tissue-related s
atiety factor for the pathogenesis of obesity, and the possible nature
of the factor are discussed.