The present study reports for the first time on the analysis of the possible origin of single-base mutations along the highly mutable human dystrophin gene. Seventy-two mutations were considered and analyzed for consistency with the "slipped-mispairing" and "hypermutable CpG" models of mutagenesis. Moreover, repeated and symmetric elements, which could participate in the formation of secondary structures, were searched in each stretch of sequence including a given mutant base. Unexpectedly, the frequency of CpG mutations was found less than reported for other genes, whereas the frequency of transitions was found to be much higher than expected. Base substitutions in CpG dinucleotides that could be explained by methylation-mediated deamination were all C-->T transitions. No G-->A transitions in CpG dinucleotides were found. A sequence motif, which has been shown to act as an arrest site for polymerase alpha, occurred associated with > 50% of single-base mutations. All the mutations but one can be explained by at least two mechanisms of mutagenesis. This would mean that mutation could occur with higher probability at a given position, when it might be produced independently by different mechanisms. According to the present data, direct or inverted repeats seem to play a major role in this context. Therefore, the search for repeats along the dystrophin gene might help in identifying potential sites of mutation.