Abstract: Small amounts of DNA circulate freely in plasma or serum, but the mechanism of release is not known. To determine if DNA is actively excreted from viable cells, we utilized real-time PCR to measure the proportion of Alu repeat sequences compared to the β-globin gene in serum and lymphocyte DNA in 27 cancer patients and 22 healthy controls. The proportion of Alu compared to β-globin was significantly greater in serum DNA than in lymphocyte DNA both in control subjects (p= 0.003) and in cancer patients (p < 0.001). Overall, the proportion was similar in cancer and control patients (p= 0.79). Further experiments showed that the β-globin gene was not more vulnerable to degradation by nuclease action than Alu sequences. Our results lead us to conclude that active DNA release is likely to play a significant role in the origin of circulating DNA.