The principle objective of this investigation was to develop an understanding of the biochemical and physiological response of free-ranging adult polar bears (<i>Ursus maritimus</i>) to prolonged fasting. A body condition index was developed from two measures, total body mass and straight-line body length, and was used as a covariate in the analyses of all other data. Protein and amino acid catabolism and urea synthesis were significantly lower in fasting bears when compared to feeding bears, and in fat bears when compared to lean bears. The inference from these results is that the energy metabolism in both states (fasting and fat) is one in which lipid is the predominant fuel for energy and nitrogen is conserved. Nutritional state (feeding versus fasting) had no significant effect on the plasma concentrations of non-esterified fatty acid, glycerol, and ketone bodies, or on the plasma ratio of acyl-carnitine to free carnitine. Furthermore, acetoacetate concentration was below the level of detection (<196 [mu]mol/L) in all bears, and â-hydroxybutyrate concentration never exceeded 291 [mu]mol/L. These results suggest polar bears are able to regulate closely the synthesis, release, and use of lipid metabolites without significant alteration in their plasma concentrations. Fasting polar bears showed no evidence of essential fatty acid (EFA) deficiency; the proportions of the diet-derived EFA linoleic (18:2[omega]6) and á-linolenic (18:3[omega]3) acids in the plasma and adipose tissue of fasting polar bears were greater than that in feeding polar bears. Plasma triiodothyronine concentrations and rectal temperatures were lower in fasting bears captured during summer-fall than in feeding bears, which suggests metabolic rates were decreased during fasting to conserve body fuels. Liver glycogen concentrations were found to be higher in fasting polar bears than in feeding bears. Furthermore, the results from intravenous administration of glucose (glucose tolerance test) to polar bears indicated the rates of insulin secretion and clearance in polar bears were slow relative to rates reported for other mammals. The inference from these results is that polar bears are not as dependent on glucose for energy as are other mammals and, as a consequence, are more lax in regulating their body glucose stores.