Although the mutagenic acridines intercalate into DNA it is not known whether such non-covalent interactions are the cause of frame shift mutations. The possibility that free radical metabolites of acridines are responsible for the mutagenicity of these agents has therefore been examined. Results show that free radical intermediates are formed when quinacrine and 9-aminoacridine are incubated with either the horseradish peroxidase/H202 or the prostaglandin synthetase/arachidonic acid system. Covalent binding of acridines to microsomal membranes was detected in the presence of NADPH.