Several recent studies have shown that liver injury is associated with the release of DNA from hepatocytes. This DNA stimulates innate immunity and induces sterile inflammation exacerbating the liver damage. Similar mechanisms have been described for acute renal injury. Deoxyribonuclease degrades cell-free DNA and can potentially prevent some of the induced tissue damage. In this study the effects of thioacetamide-induced hepatorenal injury on plasma DNA in rats were analysed. Plasma DNA of both nuclear and mitochondrial origin was higher in thioacetamide-treated animals. Administration of deoxyribonuclease resulted in a mild non-significant decrease of total plasma DNA and plasma DNA of mitochondrial but not of nuclear origin. This was accompanied by a decrease in bilirubin as well as in creatinine and blood urea nitrogen as markers of renal function. In conclusion, our study confirmed the hepatotoxic and nephrotoxic effect of thioacetamide. The associated increase in cell-free DNA seems to be involved in the pathogenesis as treatment with deoxyribonuclease resulted in a partial prevention of the hepatorenal injury. Further experiments will focus on the effects of long-term treatment with deoxyribonuclease in other clinically more relevant models. Clinical studies should test endogenous deoxyribonuclease activity as a potential risk determinant for kidney or liver failure.