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5-Methylamino-2'-deoxyuridine (I) was shown to be a specific ant ¡herpes agent with very low toxicity in cell cultures and chick embryo. It has no activity against other DNA viruses like vaccinia, and adeno 2. Replacement of the 5-methylamino group in I with 5-ethylamino and 5-dimethylamiim resulted in reduction of potency and selectivity. The 5-amino, 5-hydroxy, 5-diazo, and 5-(N-acetylmethylaniino) analogs are inactive. Some physical and biochemical properties of I are described. A tritium-labeled I was prepared for incorporation study.The effectiveness of using nucleoside antimetabolites as selective antiviral agents was well demonstrated by the clinical efficacy of o-iodo-2'-deoxyuridine (idoxuridine) in the treatment of herpes keratitis.1-4 While the mechanism of antiviral action of idoxuridine, and of the more recently described 5-trifluoromethyl-2'-de-

chondria were used immediately after isolation. All data are based on from two to five independent determinations.The data reveal that the uncoupling efficiency of a given concentration of DNP depends upon the substrate metabolized. At 5 X 10~~6 M, DNP uncoupled approximately 50% of the phosphorylation associated with -ketoglutarate oxidation. This same concentration of DNP had relatively little effect on the phosphorylation coupled with the oxidation of «-glycerophosphate, succinate and glutamate. At a higher level of DNP, 1 X 1CU4 M, phosphorylation associated with «ketoglutarate oxidation was almost completely eliminated. In contrast, phosphorylation coupled with glutamate oxidation was only slightly reduced. With the respiratory substrates, succinate and «glycerophosphate, moderate decreases in the phosphate esterified were observed. Neither concentration of DNP caused marked alterations in the respirator)7 rate. Other experiments with a further five-fold increase in DNP, 5 X 10~4 M, completely uncoupled phosphorylation with all substrates.