THERE have been several different approaches to the stereochemistry of the interaction of actinomycin and DNA, including studies of the interaction of DNA-like polynucleotides with actinomycin1,2, and of DNA with model compounds related to actinomycin3–5, using various experimental techniques. Reports on the optical rotatory-dispersion (ORD) and circular dichroism (CD) data for the actinomycin–DNA complex and for actinomycin alone6–9, as well as unpublished results from this laboratory, indicate that the rotational strength of the optically active transitions—which can be ascribed to the dimethylaminophenoxazone chromophore of actinomycin—in the visible region of the spectrum increases in the presence of DNA. The molecular mechanism of the interaction of actinomycin with DNA is still obscure, however, for the increase in optical activity could result from a change in the conformation of actinomycin in the presence of DNA and/or from the perturbing influence of the asymmetric environment (DNA) on the chromophore transitions of actinomycin.