We have found recurrent chromosome breaks at a site (the "fragile site") on the long arm of chromosome 16. This site segregates in simple Mendelian dominant fashion in a large family. The distal portion of the chromosome sometimes shows selective endoreduplication. Preliminary linkage results reveal only 3 recombinants in 33 opportunities for recombination between the fragile site and the alpha locus of haptoglobin, an indication that the alpha-Hp gene is located near this region on chromosome 16.