The informational aspects of nucleic acid synthesis have attracted much more attention than the quantitative significance of DNA, rRNA, tRNA, and nucleotide synthesis. Animal and human studies suggest that in energetic terms, 5-10% of the energy used in synthesising tissue protein is expended in manufacturing an appropriate amount of synthetic machinery, that is the ribosome and tRNA. The two sources for synthesis of nucleotides are salvage of nucleotides released by intracellular degradation or derived from the diet, and nucleotides synthesised de novo from amino acids (for example, glutamine) and sugars (glucose). The comparative importance of these two processes is not well defined, but rRNA production requires a high de novo input in cell types with the capacity for rapid division (for example, lymphocytes). The gut is unusual in requiring a ready arterial supply of nucleotides synthesised by hepatic de novo pathways. Animal studies show that an exogenous supply of nucleotides (salvage) can improve liver regrowth, immune responsiveness to a microbial challenge, and gut morphology in diarrhoea models. Humans adapt to dietary nucleotide intake by downregulating de novo pathways. All total parental nutrition regimens, and most enteral regimens lack nucleotides, which may predispose to an inadequate supply of preformed nucleotides to gut and immune cells in the critically ill, artificially fed patient. Unfortunately, there are no clinical studies that answer this point at present.