The sequence analysis of Ig variable region genes transcribed within different B-cell subpopulations from human tonsil led us to identify a rare DNA sequence modification event consisting of bp insertions and/or deletions (I/D). Although these events were previously reported, they had never been formally associated with the somatic hypermutation process. I/D events share with more conventional somatic hypermutation events their localization within hypervariable regions and, most particularly, within DNA motifs known to be mutational hot spots. Repetitive DNA tracts or DNA elements capable of forming DNA loop intermediates seem to be the preferred substrate for I/D to occur. These characteristics suggest a model for somatic hypermutation reminiscent of the "polymerase slippage" model involved in replication and repair mutations in prokaryotes, yeast, and mammals.