Skeletal anomalies present in trisomy 16 in the mouse--an animal model of human trisomy 21--are described. Altogether 27 fetuses with trisomy 16 and 118 chromosomally balanced siblings were examined radiographically and by alizarin staining on day 20 of gestation; the radiographs were analyzed by computer-aided densitometry and structural differentiation. Extensive asymmetry or abnormal fusion of the vertebral centers and alterations of the vertebral arches were observed along with rib malformations (rib-vertebra syndrome). The skull primarily exhibited anomalies of the occipital bone. Ossification of the humerus, femur, and tibia was characterized by reduced mineralization. Typical, fracture-like alterations affecting only the tibia were also observed. Measurement of the lengths of the humeri of fetuses of comparable weight revealed a growth retardation not correlatable with the degree of mineralization. The significance of these skeletal abnormalities with regard to the trisomy 21 syndrome is discussed.