Inosine is deaminated adenosine. Inosine is enzymatically introduced in some plant tRNAs but not in other RNAs or DNA. Nonetheless, our data show that RNA and DNA from Arabidopsis thaliana contain (deoxy)inosine, probably derived from non-enzymatic adenosine deamination in nucleic acids and usage of (deoxy)inosine triphosphate (ITP / dITP) during nucleic acid synthesis. We identified a plant INOSINE TRIPHOSPHATE PYROPHOSPHATASE (ITPA) which is conserved in many organisms. Arabidopsis ITPA dephosphorylates deaminated nucleoside di- and triphosphates to their respective monophosphates. ITPA mutation causes inosine di- and triphosphate accumulation in vivo and an elevated (deoxy)inosine content in DNA and RNA. Cadmium-induced oxidative stress, known to foster deamination, leads to more ITP in the wildtype and especially in itpa mutants suggesting that ITP originates from ATP deamination. By contrast, erroneous IMP phosphorylation by AMP kinases seems not to be a major ITP source in vivo although these enzymes phosphorylate IMP in vitro. Mutation of ITPA causes salicylic acid (SA) accumulation, early senescence and upregulation of transcripts associated with immunity and senescence. ITPA is part of a molecular protection system, preventing accumulation of (d)ITP, its usage for nucleic acid synthesis, and probably nucleic acid stress leading to SA accumulation, stress gene induction and early senescence.