This article has attempted to point out some of the relationships between 5-HT and catecholamine (NE, DA) neurons in brain and the control of appetite and food intake. At least two bodies of evidence support this connection. The first is pharmacologic, and demonstrates that drugs that stimulate transmission across 5-HT and/or catecholamine synapses suppress hunger and food intake. The second is physiologic and metabolic, and reveals that the ingestion of foods, on either an acute (single meal) or chronic basis, can reliably modify the uptake of TRP and TYR into brain (and hypothalamus), and directly alter the synthesis of their transmitters (5-HT and the catecholamines, respectively). The synthesis of these two bodies of information has led to models by which (1) changes in dietary carbohydrate ingestion, by modifying brain TRP uptake and 5-HT production, may cause like changes in 5-HT release, and in the stimulation of 5-HT receptors in brain circuits that control carbohydrate appetite, and (2) dietary protein intake, by altering brain TYR uptake, directly influences DA and NE synthesis (notably in hypothalamus), perhaps providing a signal to brain circuits monitoring dietary protein adequacy regarding protein intake. In this case, one might imagine that stimulating DA and/or NE receptors in such circuits might suppress protein intake, a possibility we are now examining in rats. As indicated in the Introduction, the broader issue being touched upon in this article concerns the body's need to acquire and maintain an optimal (or adequate) nutritional balance (for growth and ultimately, reproductive success). Rats and humans evolved in an environment that does not provide continuous access to all essential nutrients, and one that presents nutrients in a complex matrix (other animals, plants) that can also include toxic compounds. Together with the fact that animals and humans do not carry a guidebook to healthy eating, we must presume that the brain mechanisms that have evolved to optimize the acquisition of essential nutrients are 'automatic' (i.e., not conscious) and quite complex. In this context, the relationships described here must be viewed as rudimentary, touching only a small portion of this complex regulatory mechanism. The hope is, as further insights develop, that we will gain a better understanding of the workings of these mechanisms, and also be able to apply this knowledge to the development of better pharmacologic (and other) aids for controlling appetite and obesity in our modern, man-made environment.