The purpose of this article is to describe briefly themethods by which the intra-mitochondrial volume may be measured both in vitro and in situ, to summarise the mechanisms thought to regulate the mitochondrial volume and then to review in more detail the evidence that changes in the intra-mitochondrial volume play an important part in the regulation of liver mitochondrial metabolism by glucogenic hormones such as glucagon, adrenaline and vasopressin. It will be shown that these hormones cause an increase in matrix volume sufficient to produce significant activation of fatty acid oxidation, respiration and ATP production, pyruvate carboxylation, citrulline synthesis and glutamine hydrolysis. These are all processes activated by such hormones in vivo. I will go on to demonstrate that the increase in matrix volume is brought about by an increase in mitochondrial [PP_i]. This is able to stimulate K⁺ entry into the matrix, perhaps through an interaction with the adenine nucleotide translocase. The rise in matrix [PP_i] is a consequence of an increase in cytosolic and hence mitochondrial [Ca²⁺] which inhibits mitochondrial pyrophosphatase. In the finalsection of the review I provide evidence that changes in mitochondrial volume may be important in the responses of a variety of tissues to hormones and other stimuli. I write as a metabolist with a working knowledge of bioenergetics rather than the converse, and this will certainly be reflected in the approach taken. If I cause offence to any dedicated experts in the field of bioenergetics by my ignorance or lack of understanding of their studies I can only offer my apologies and ask to be corrected.