I n vitro experiments to study interaction of the mutagenic flavonoid quercetin with DNA are described. Calf thymus DNA treated with quercetin for various time periods was subjected to S1 nuclease hydrolysis. Thermal melting profles of treated DNA were also determined using St nuclease. The rate of DNA hydrolyzed after 1 hr of pre-treatment with quercetin was found to be only about 50% of that in its absence. However, after 10 and 24hrs of treatment with the drug, the rate of S1 nuclease hydrolysis was observed to be greater than that of native DNA. Thermal melting profiles of DNA, treated with quercetin for 10 and 24 hrs, indicated a slight decrease in melting temperatures. Gel filtration of native DNA, which had been digested with S1 nuclease after preincubation with quercetin for 24 hrs, indicated the production of various sized degraded molecules. The results suggest that the initial interaction of quercetin with DNA may have a stabilizing effect on its secondary structure, but prolonged treatment leads to an extensive disruption of the double helix.