The Kniest syndrome is a newly defined chondrodystrophy consisting of disproportionate dwarfism with kyphoscoliosis, flat facies with prominent eyes, myopia, cleft palate, hearing loss and limited joint motion. As a result of a collaborative study of 12 patients, the radiographic features of this syndrome have been found to be diagnostic. The major radiographic features consist of: flat, markedly elongated irregular vertebral bodies, which have superior inferior defects in their midportion during infancy and early childhood. Dumbbell shaped long bones which in later life show epiphyseal ossification delay and irregularity, as well as expanded metaphyses with a cloud like effect on both sides of the epiphyseal plate. Characteristic flattened and squared off epiphyses of the hands with joint space narrowing. Biopsies of costochondral junction and iliac crest reveal identical histologic and ultrastructural abnormalities which differ from all other chondrodystrophies. Throughout the cartilage are large hypertrophic cells whose surrounding matrix is loose and irregular in staining ability with large holes resembling Swiss cheese. The Kniest syndrome represents a distinct chondrodystrophy diagnosable radiographically and associated with specific abnormalities in cartilage structure.