This technique was developed to screen for point mutations, but deletions and insertions too small to be recognized by gel electrophoretic techniques are also detected. Whereas earlier techniques are able to detect point mutations, not all mutations were detected and/or the technique was not convenient or direct (reviewed in 1). The chemical cleavage of mismatch method (CCM) rapidly and reliably detects all classes of point mutations (2). Reference DNA probe is mixed with excess test DNA or RNA; the mixture is melted, and then cooled to allow reannealing and, thus, heteroduplex formation with mismatched or unmatched base pairs at the position of the mutation. Probe is modified at mismatched C and T bases by reaction with hydroxylamine and osmium tetroxide, respectively, and subsequently cleaved by piperidine treatment. Fragments are sized on gels (of the type needed for sequencing) to locate the point of cleavage and, hence, the mutation. In the case of point mutations, mismatched G and A bases will not be directly detected, but they are transposed to mismatched C and T bases, respectively, by use of probe of opposite sense for detection. However, matched bases adjacent or close to mismatched or unmatched bases become reactive by transmission of the distortion (2,3), and can signal the presence of the mutation and hence allow indirect detection. This allows detection of insertions (3). Unmatched C and T bases are also reactive, allowing detection of deletions.