We previously reported on a 43-year-old patient with Wiskott-Aldrich syndrome (WAS) who experienced progressive clinical improvement and revertant T-cell mosaicism. Deletion of the disease-causing 6-bp insertion was hypothesized to have occurred by DNA polymerase slippage. We now describe 2 additional patients from the same family who also had revertant T lymphocytes that showed selective in vivo advantage. Somatic mosaicism was demonstrated on leukocytes cryopreserved in the first patient when he was 22 years old, 11 years before his death from kidney failure. The second patient is now 16 years old, has a moderate clinical phenotype, and developed revertant cells after the age of 14 years. These results support DNA polymerase slippage as a common underlying mechanism, and they indicate that T-cell mosaicism may have different clinical effects in WAS.