Parenteral administration of folic acid to rats produces marked increases in the rates of synthesis of protein, RNA and DNA in the kidney. Basic nuclear protein synthesis is increased within 1 hour of folate administration with a sharper increase appearing about 18 hours and reaching a maximum about 26 hours. RNA synthesis increases to reach a maximum a t 12 hours after folate before declining to normal levels a t 24 hours. The increase in the rate of DNA synthesis commences a t about 18 hours and reaches a maximum, about 20 times above control levels, about 32 hours after folate.Using the increased rate of DNA synthesis normally seen 26 hours after folate as a reference point, actinomycin D was found to produce a very marked depression of .DNA synthesis when administered between 0 and 4 hours after folate ; a t longer time intervals this depression became less marked and when actinomycinD was given a t 20 hours no effect was observed. ActinomycinD, given a t the same time as folic acid, also abolished the increase in the rate of RNA synthesis normally seen 12 hours after folate.In contrast to the time dependent effect of actinomycin D, cycloheximide produced a similarly profound decrease in the rate of DNA synthesis, measured 26 hours after folate, when the drug was given at any time between 0 and 25 hours after folate.These results suggest that the complete requirement for increased RNA synthesis has been met by the time that increased DNA synthesis begins a t 18 hours after folate administration, but that there is continuous need for newly synthesised protein both before and during the period of increased DNA synthesis.Increases in RNA and DNA Synthesis can be induced in the rat kidney by a single intravenous injection of folic acid (250 pg/g body weight) [l]. This effect is characterized by a rapid increase in the rate of incorporation of [3H]thymidine into rat kidney DNA beginning a t about 18 hours, reaching a maximum at 32 hours and returning to normal within 6 days [2]. Autoradiographic studies show a large increase in the number of [3H]thymidine labelled cells in the renal tubules, also commencing a t about 18 hours, which is followed several hours later by a wave of mitotic activity [2]. A similar pattern of response has been obtained in mice [3]. The sharp peaks in rate of DNA synthesis and in numbers of labelled cells and of mitoses suggest a high degree of synchrony in the proliferative response of the renal t.ubular cells to folic acid. Thus the folate-stimulated kidney represents a potentially valuable system for the study of some of the factors involved in the induction of DNA Synthesis and mitotic activity. I n this paper some of the biochemical changes which occur in the folate-stimulated kidney, both before and during the period of increased DNA synthesis, are described. I n an attempt to examine the possible inter-relationships between changes in the rates of RNA and protein synthesis and the rise in DNA synthesis the effects of two antibiotics, actinomycin D and cycloheximide, which inhibit ...