Two matrices, 4-phenyl-α-eyanocinnamic acid (PCC) and 4-benzyloxy-α-eyanocinnamic acid (BCC), were identified for the determination of polycyclic aromatic hydrocarbon (PAH) adducts of DNA bases by matrix-assisted laser desorption ionization. These matrices were designed based on the concept that the matrix and the analyte should have structural similarities. PCC is a good matrix for the desorption of not only PAH-modified DNA bases, but also PAHs themselves and their metabolites. Detections can be made at the femtomolar level.