Mice trisomic for Chromosome (Chr) 16 have been used extensively as an animal model for human Down Syndrome (Trisomy 21). This system has drawbacks, however: trisomy for all of Chr 16 is incompatible with postnatal survival and produces trisomy for many more genes than those conserved in human Chr 21. We report here the development and preliminary characterization of mice that are trisomic for only the segment of mouse Chr 16 that is conserved in human Chr 21. While these segmentally trisomic mice, Ts(17(16)) 65Dn, do not appear to have all the features characteristic of Down Syndrome, they represent a mouse model that survives to adulthood and may be useful to study features of Down Syndrome that develop later in life, such as susceptibility to infection, increased incidence of leukemia, and Alzheimer-like neuropathology.