It is now well established that deoxyribonucleic acid* is the molecular counterpart of the genetic apparatus. In this two-stranded helical polynucleotide the perfect crystalline geometry which normally prevails requires that adenine residues in one chain be hydrogen-bonded to thymine residues in the other; similarly, guanine residues can only be hydrogen-bonded to cytosine residues.'-'Thus, one chain is necessarily the complement of the other, and it appears likely that each chain serves as the template for the synthesis of its complement. 4-6 Current views on the molecular basis of mutations hold that they are due to a variety of alterations in the nucleotide sequence within the two-stranded DNA helix. Presumably, many of these alterations arise from mistakes made during its replication. It appears from studies of fine structure genetics7'8 that such mistakes could involve the substitution of noncomplementary bases, and also the addition or deletion of one or a sequenceof nucleotides, during the synthesis of a progenychain on its template. In view of these plausible mechanisms of mutation, we have examined the possibilities whereby noncomplementary base pairs can be accommo-dated within the two-stranded helical framework of DNA. We first investigated the effects of varying proportions of noncomplementary bases incorporated into pairs of complementary polyribonucleotides whichare known to form two-stranded helices like DNA. The results of such experiments allowed us to exclude the notion that noncomplementary bases remain within the interior of the helix. Instead, they suggested that noncomplementary nucleotidesof opposite chains rotate out of the helix in such a manner as to enable normal hydrogen-bonded base pairing of subsequent regions of nucleotides whichare in register. This structural alternative was then explored by model building and found to be readily plausible. Experimental Approach.-Polyadenylic and polyuridylic acids* are single stranded polyribonucleotides9''containing base residues equivalent to the complementary pair, adenine-thymine. present in DNA. Indeed, in neutral saline solution they form a 1: 1 two-stranded helical complex which has essentially the same structure as DNA."-" Underappropriate conditions, a second strand of poly U can beinduced to wrap aroundthis poly (A+ U) helix, so that a three-stranded com-plex is formed in which the molar ratio of adenine to uracil is 1: 2.13