Adrenalectomy of gold thioglucose (GTG)-treated hyperphagic obese mice had been shown by us earlier to result in anorexia, weight loss, hypoglycemia and subsequent death of all mice. More recent studies suggest that adipose tissue mass may not be the critical determinant of anorexia since a large proportion of GTG-treated non obese (pair-fed to curb obesity) mice when challenged with adrenalectomy also developed anorexia. The aim of the present studies was to determine whether the changes in circulating metabolites, namely, glucose, free fatty acids and hormones, including insulin, glucagon and ACTH, which accompany adrenalectomy, might provide a clue to the causative agent for the onset of anorexia in GTG obese and non obese mice. Accordingly, plasma levels of glucose, free fatty acids, insulin, glucagon and ACTH were measured in GTG-treated obese, non obese and in normal untreated mice following adrenalectomy or a sham operation. Preoperatively, plasma insulin levels were significantly elevated in GTG obese mice whereas plasma glucose, free fatty acids and glucagon levels were not appreciably different than those of untreated controls. Upon adrenalectomy and onset of anorexia, GTG obese mice exhibited a progressive decline in blood glucose and insulin levels; plasma free fatty acids increased precipitously but only after the first day. Plasma glucagon levels declined immediately following adrenalectomy, however, by the 6th day postoperatively they were significantly elevated above the sham operated obese and untreated controls. Prior to adrenalectomy, the pair-fed GTG non obese mice exhibited blood glucose and insulin levels well below the levels of untreated controls and GTG obese mice whereas plasma free fatty acids and glucagon levels were markedly elevated.(ABSTRACT TRUNCATED AT 250 WORDS)