We found deletions involving the retinoblastoma gene in 12 of 49 tumors from patients with retinoblastoma or osteosarcoma. After mapping the deletion breakpoints, we found that no two breakpoints coincided. Thus, our data do not support the conclusions of others regarding the existence of a "hotspot" for deletion breakpoints in this gene. In 4 of the tumors, we sequenced 200 base pairs surrounding each deletion breakpoint. Three deletions had termini within pairs of short, direct repeats ranging in size from 4 to 7 base pairs. These results indicate that the "slipped mispairing" mechanism may predominate in the generation of deletions at this locus. Our review of deletion breakpoints at other genetic loci reveals that the nature of the sequences present at deletion breakpoints (short, direct repeats versus middle repetitive elements) varies according to the genetic locus under study.