Mannoheptulose (2g/kg i.p.) increases serum glucagon and decreases serum insulin via its effect on pancreatic islet cells. These changes in endogenous hormone status had effects on rat liver mitochondria that were comparable to the effects of injecting porcine glucagon (0.5 mg/kg i.p.). Mitochondrial adenine nucleotide content was increased 38 or 39% by mannoheptulose or glucagon respectively, citrulline synthesis by 165 or 193%, pyruvate carboxylation by 113 or 135%, coupled respiration by 34 or 42%, and uncoupled respiration by 40 or 54%. We conclude that the reciprocal changes in endogenous insulin and glucagon brought about by mannoheptulose offer a useful and interesting alternative to glucagon injection for studying the effects of these pancreatic hormones on liver mitochondria.