The clinical manifestations of osteofluorosis in subjects exposed to high levels of fluoride in air or drinking water for longer than 10 years were observed. In particular, the relationship among the findings observed in X-ray pictures of bone and the extent of fluoride exposure, and the concentrations of fluoride in serum, urine and the environment were studied. Interpretation of the film was carried out by orthopedic surgeons by means of blind tests. When sclerotic changes of bone at more than two locations were observed, the subject was diagnosed as having possible osteofluorosis. From these studies, the following conclusions were obtained. 1) Of the 63 subjects exposed to airborne fluoride (average concentration: 0.88 +/- 0.74mg/m3; max.: 2.9mg/m3) for longer than 10 years, four possible cases of osteofluorosis were found. However, there were no patients presenting typical osteofluorosis. The average fluoride concentrations in serum and urine of the exposed group were 0.055 +/- 0.045ppm and 2.99 +/- 2.20ppm, respectively. The values were almost twice as high as those found in the control group (47 subjects). 2) Of the 95 residents in areas where the concentration of fluoride in drinking water was high (area A: 1.0-3.2 ppm and area B: 2.0-13 ppm), 19 subjects were diagnosed as possible cases of osteofluorosis and one case of definite osteofluorosis (corresponding to the second phase of the Roholm's classification) was found. In the latter case, the subject had drunk highly contaminated (12ppm) water for 26 years; a high serum fluoride concentrations (0.427ppm) and high levels of ALP and osteocalcin were found. This is one of the rare cases of osteofluorosis in Japan; only a few cases have been reported in the past. 3) As primary signs of changes in bone due to osteofluorosis, as seen in X-ray pictures, osteophytes of the lumbar vertebrae, ossification of the pelvic obturator membrane and ligaments and ossification of the interosseous membranes of forearms and lower legs are emphasized.