Failure to clear self nucleic acids is thought to drive pathological inflammation in diseases such as systemic lupus erythematosus and polyarthritis. In support of this, Dnase2−/− mice (whose phagocytes cannot digest engulfed DNA) die during embryonic development owing to the overproduction of type I interferons (IFNs). In addition, although Dnase2−/− mice with defects in IFN signalling are viable, they develop severe arthritis. Ahn et al. show here that pathological inflammation in these mice is driven by activation of the cytoplasmic DNA sensor STING (stimulator of IFN genes). They found that DNA from necrotic or apoptotic cells induced pro-inflammatory cytokine production by myeloid cells in a STING-dependent manner. The authors next generated Dnase2−/−Sting−/− mice; these animals survived birth, grew normally and did not develop polyarthritis. Similarly to Dnase2−/− macrophages, Dnase2−/−Sting−/− macrophages could not digest engulfed nuclei from apoptotic thymocytes. So, potentially harmful self DNAs still accumulate in Dnase2−/−Sting−/− mice, but they do not drive pathological inflammation.