Chronic renal failure (CRF) inhibits the ability of the kidneys to excrete fluoride. Increased systemic fluoride, has been shown to result in increased thickness of the growth plate (GP). Severe CRF also leads to widening of the GP in uremic rats. Therefore, we hypothesize that fluoride exposure may further accentuate the widening of the GP induced by uremia. Objectives: To determine whether the fluoride supplementation affects growth plate disturbances in uremic rats. Methods: Young rats (100 gm) were divided into four groups: sham-operated (S), S with 50 ppm F in the drinking water (F), 5/6 nephrectomy (Nx), and Nx with F. After 2 weeks the animals were sacrificed, and 1 femoral epiphysis from each animal was analyzed for fluoride, while the other was fixed in 10% formalin and processed for histomorphometry. Results: Mean ± SD ppm fluoride in the femoral GP of the S group was 546 ± 122; the Nx group was 684 ± 125; the S +F group was 1445 ± 178; the Nx+F was 2767 ± 403. ANOVA showed statistically significant differences between the groups. Fluoride supplementation increased the thickness of the GP when compared to S animals. The thickness in the GP was increased further by NX and further widened in the Nx + F group. The thickness in the GP affected by F occurred primarily in the hypertrophic zone. Conclusions: This study suggests that in chronic renal insufficiency, fluoride supplementation enhances the widening of the epiphyseal growth plate. Further studies to determine mechanism by which fluoride affects the growth plate are needed to determine the possible role of excess fluoride supplementation on renal osteodystropy in children.