The behaviour of the in vitro-activities of an alkaline and an acid deoxyribonuclease (DNase I and II, resp.), and of an inhibitor of DNase I of the kidney of mice, as well as of the DNA- and protein-content of kidneys and thymus, was studied in about 500 mice 4 hours to 21 days after exposure to folic acid in doses of 60 — 180 mg/kg body-weight.The most important results can be summarized af follows:1. Activity of DNase I decreased and activities of DNase II and of a DNase I-inhibitor increased under the influence of high doses of folic acid. Significant effects were observed 16 — 24 hours after folic acid-injections. Extreme values (80% decrease [DNase I], 180% increase [DNase II, DNase I-inhibitor]) were reached after 2 and 4 days and were dose-dependent. Control values reappeared within 1 — 3 weeks.2. Protein- and DNA-content of the thymus behaved very similarly to DNase I-activity of the kidney.3. The increase of the DNase II-activity of the kidney under the influence of folic acid resulted from enzyme induction. As to the behaviour of DNase I loss of enzyme out of damaged cells and the induction of a DNase I-inhibitor in the kidney must be taken into account.4. In many systems DNase I may control DNA-synthesis. Preliminary studies on the behaviour of folic acid-induced reaction of the kidney, when inhibited by X-irradiation, Actinomycin D, Actidione, or poly (vinylsulfate), suggest that DNase I-inhibitor plays a certain role in combining protein- and DNA-synthesis by inhibiting DNase I.