The interactions of phenothiazine such as chlorpromazine hydrochloride (CPZ(center dot)HCl) and promethazine hydrochloride (PZ center dot HCl), with nucleic acids (NA) have been investigated. The CPZ-NA system can produce very intense resonance Rayleigh scattering (RRS), but the RRS intensity of the PZ-NA system is very weak. The energy relationship of the two reaction systems has been calculated by the AM1 and B3LYP of density functional methods for quantum chemistry, the binding site and interacting model of CPZ-NA and PZ-NA are studied. The results show that CPZ has strong binding ability with nucleic acids, but PZ hardly react with nucleic acids. It can be expected that RRS method may be a useful means for molecular recognition of nucleic acids and the molecular design of gene medicine in the future. Moreover, the method is used for the quantitative determination of nucleic acids by employing chlorpromazine hydrochloride as reagent, which has very high sensitivity and good selectivity. Therefore, a sensitive, simple and rapid new method has been developed for the determination of nucleic acids.