SynopsisDrosophila melanogaster larvæ when cultured aseptically on a synthetic diet require exogenous ribose nucleic acid (RNA) for normal growth even though they can synthesize their own endogenous RNA from simple precursors. The optimum dietary supply lies between 0.4 and 0.7 per cent RNA. Individual bases, nucleosides and nucleotides which make up RNA cannot substitute for the whole polynucleotide, but adenine, adenosine, adenylic acid, guanosine and guanylic acid are used and stimulate growth to varying degrees. The pyrimidines and their nucleosides and nucleotides are not used when fed singly.It is shown that the de novo synthesis of purines may be more difficult than that of pyrimidines, and that if a source of purines is supplied (as adenylic acid), then the nucleosides and nucleotides of both cytosine and uracil are utilized by the larvæ, whereas the free bases are not. Cytidylic and uridylic acids seem to be interchangeable, and together with an adequate supply of adenylic acid give as good growth as RNA. Orotic acid and 2—6-diaminopurine are not used by the larvæ under the conditions described, but hypoxanthine and inosine are: xanthine and xanthosine can also be shown to have an effect on growth.Dose-response curves were determined for adenylic, guanylic, cytidylic and uridylic acids under conditions which allow the determination of the optimal supplies of each. These are found to be about 0.110, 0.080, 0.025 and 0.025 per cent, respectively. The requirement of RNA is therefore primarily a requirement of adenylic acid, since more than enough of the other nucleotides should be available when the supply of RNA is optimal. The optimal supply of adenine corresponds almost exactly with the optimal supply of adenylic acid, though a somewhat delayed larval development may be a result of energy utilization in the base-nucleoside-nucleotide conversion.These results are discussed in the light of our knowledge of purine and pyrimidine utilization in other multicellular organisms, particularly the rat, and possible applications of the findings are considered.