Many aspects of the cell biology of lymphocytes and macrophages have been studied extensively over many years. Our recent work on these cells has investigated the fuels utilized, the metabolism carried out and the importance of this metabolism for the specific function of these cells in the immune system. The quantitatively important role of glutamine and the observation that both glutamine and glucose are only partially oxidized by both types of cell have been established. This work has led to a new hypothesis to explain the high rates of partial oxidation of both fuels in lymphocytes and macrophages, and in other cells such as enterocytes, colonocytes and also in neoplastic cells. In addition, the high rate of glutamine utilization and its importance in such cells has raised the question as to the source of this glutamine in the body: the evidence suggests that this is muscle. The metabolic relationship between the glutamine-producing tissue and the cells of the immune system provides an explanation for some well-established changes in metabolism during the condition of surgery, trauma, sepsis and burns. Knowledge of the metabolism of glucose, glutamine, pyruvate and long-chain fatty acids by these cells raises some intriguing questions concerning the role and function of the citric acid cycle in these and other similar cells, including tumour cells.