Changes in brain metabolites, energy balance, resting metabolic rate, body composition, and organ histology were studied over 10 days in control (C), cachectin-infused (CIR), and pair-fed (PFR) (in relation to CIR) rats. The cachectin was continuously infused for the 10 days into the superior vena cava at the rate of approximately 100 micrograms.kg-1.day-1. The brain of the CIR had significantly more tryptophan and 5-hydroxyindole-3-acetic acid than C and PFR. The CIR rats were anorexic, hypermetabolic, relatively hyperglycemic, and had raised blood urea nitrogen with comparable creatinine levels when compared with similarly wasted PFR. They had significant loss of muscle mass, especially in muscles with a predominance of type II fibers. However they gained liver, heart, and lung mass. The loss of muscle mass could be ascribed to dietary deficiency, but the gain in visceral mass was associated with an increase in organ DNA and protein. Histology showed that there was cell proliferation in the liver, heart, and kidneys. The data are consistent with centrally mediated anorexia with nutritionally mediated muscle wasting but with visceral hypermetabolism, protein accumulation, and cell proliferation.