Primary synovial chondromatosis (PSC) is thought to be a cartilaginous metaplasia, but it may recur locally and malignant change has been reported. Histologically, the cartilage is usually cellular, with binucleate forms. These findings suggest that the disease is not simply a metaplasia but imply a proliferative component. In this study, immunohistochemical detection of Ki-67 protein using an antigen retrieval microwave heating technique and DNA image cytometry (VIDAS image analysis system) has been used to assess the proliferative activity in 20 cases of PSC and the results have been compared with those obtained in other cartilage tissues: ten enchondromas, ten chondrosarcomas, and ten samples of normal articular cartilage. There was no detectable staining for Ki-67 protein in cases of PSC or in benign tissues, but there was a significant association between Ki-67 labelling index and grade in the chondrosarcomas (P < 0.01). The absence of mitotic figures and the lack of Ki-67 protein in PSC are consistent with a metaplasia. All enchondromas gave diploid DNA histograms but non-diploid histograms were obtained i eight cases (40 per cent) of PSC, with significant populations of hyperdiploid and DNA aneuploid cells. The mean DNA content, the percentage of hyperdiploid cells, the percentage of DNA aneuploid cells, and the 2c deviation index were all significantly higher in PSC than in enchondromas (P < 0.01). These findings with image cytometry suggest a proliferative process in the development of at least some cases of PSC. In terms of cell proliferative activity, PSC appears to occupy a position which is intermediate between benign enchondromas and malignant chondrosarcomas, which may explain the aggressive clinical behaviour occasionally seen in this condition.