The binding of distamycin and netropsin to duplex DNA has been studied by Raman spectroscopy. Several changes occur in the Raman spectra of these drugs upon binding DNA. These changes were analyzed by assigning specific motions to the observed Raman bands through the use of molecular subunits of the drugs and normal mode calculations. Our Fig. 1.) Netropsin samples, available in both sulfate and hydrochloride forms, were purified by repeated recrystallization into the sulfate form. Various concentrations of the drug were used up to its solubility limit. At room temperature this was about 0.7 mg/ml. The distamycin A samples required no purification to obtain high-quality spectra. Because the solubility of distamycin A is much greater than that of netropsin, concentrations up to 2.5 mg/ml could be used. Spectra were obtained from 100 to 2000 cm-l. Care was taken to minimize the length of time the samples were irradiated by the laser. Raman spectra obtained at 250 and 10C were not significantly different. Laser irradiation had no effect on the ultraviolet absorbance spectra of the samples. The drugs were dissolved in a 3-4 mM NaCl solution at pH 6.0-7.0. Calf thymus DNA, obtained from Sigma, was extracted with chloroform and sonicated, then extensively dialyzed with 1.0 mM NaCI. It was rotoevaporated to dryness and redissolved with double-distilled water to a final concentration of 6.0 mg/ml. The