In chronic renal insufficiency (CRI), serum levels of fluoride (F-) are elevated. However, there is limited information about the effects of F- on bone in CRI. In this study, we determined whether F- content in mineralizing tissue (growth plate, cortical bone, and bone marrow of the femur) is affected by uremia. Adult rats were divided into two groups [sham-operated (S) and 5/6 nephrectomized (Nx)]. At sacrifice, the serum creatinine (mg/dl) in the S and 5/6 Nx animals was 0.37+/-0.09 (mean+/-SD) and 1.10+/-0.34 at 4 weeks, and 0.38+/-0.04 and 0.90+/-0.36 at 8 weeks, respectively. The serum calcium, phosphorus, and parathyroid hormone levels were lower and the serum 1, 25-dihydroxyvitamin D levels were higher in S animals than Nx animals at both 4 and 8 weeks. F- urinary excretion (ppm/24 h) was reduced in Nx animals at 4 weeks (34.0+/-19.2) versus S animals (50.7+/-12.9) (P<0.05). F content (ppm) was significantly increased in the growth plate in Nx animals compared with S animals both at 4 weeks (550+/-167 vs. 353+/-63) and at 8 weeks (654+/-135 vs. 396+/-97), respectively (P<0.01). The F- content in cortical bone was similarly increased in Nx animals compared with S animals, but was only statistically increased at 8 weeks. There was no difference in bone marrow F- content between the two groups. In conclusion, this study suggests that in CRI, there is a rapid increase in F- content of the distal femur in the growth plate region, with a subsequent slower increase of F- content in cortical bone.