This study presents the results of light- and electron-microscopic and enzyme histochemical investigations in ten cases of congenital pseudarthrosis of the lower limb. At the time of surgery, six of the ten patients had not been operated on previously. The characteristic histological feature of the "sclerotic type" of congenital pseudarthrosis was a marked fibromatous reaction consisting of cellular connective tissue. The constituent cells were arranged in bundles and had elongated nuclei. The number of nuclei per visual field was considerably higher in pathological specimens than in specimens from the uninvolved leg. In places, the histological appearance resembled somewhat that of palmar fibromatosis (Dupuytren's disease). Destruction and absorption of bone were always found. Electron-microscopic analysis showed that a large number of the cells represented myofibroblasts. These findings were supported by the positive reaction of the cells for the enzyme diaminopeptidase IV, a marker enzyme for myofibroblasts [30]. As yet it is not possible to decide whether the constriction of the pseudarthritic bone is caused by a thickened myofibroblast-containing periosteum [40] or by the aggressive osteolytic component of the fibromatosis [12, 19, 41]. Furthermore, the relationship of congenital pseudarthrosis to fibrous dysplasia of bone is still unknown. Obviously, there are histological similarities between the two diseases, including the presence of osteolytic fibrous tissue in the medullary cavity and C-shaped bone trabeculae. However, the pattern of bone involvement and prognosis are different. Irrespective of the type of congenital pseudarthrosis, focal angiomatous hyperplasia was noted in some cases. This proliferation of blood vessels is most likely a reactive change.(ABSTRACT TRUNCATED AT 250 WORDS)