This study was conducted to find out the possible underlying mechanism of various manifestation of fluorosis, a disease caused by excess ingestion of fluoride. For this the fluoride belt of Jaipur district was selected. The parameters selected were serum Parathyroid hormone, the levels of which are directly affected by fluoride intake. The levels of serum seromucoid, serum and leucocyte ascorbic acid, serum sialic acid (SSA) reflects ground substance metabolism. The study was conducted on two hundred children, selected from four areas (50 from each area) consuming water containing 2.4, 4.6, 5.6 and 13.6 mg/l of fluoride. Drinking water fluoride and serum fluoride were measured by Ion selective electrode method. Serum parathyroid by RIA and all other parameters were measured spectrophotometrically. The results revealed an increase in levels of fluoride, parathyroid hormone and seromucoid in serum with increasing water fluoride concentrations. Serum Calcium and serum ascorbic acid were found in normal range, how ever leucocyte ascorbic acid were decreased. A high positive correlation among fluoride concentration in drinking water and serum parathyroid hormone (r=0.967), and, serum parathyroid hormone and serum seromucoid concentration (r=0.935) was also observed The results indicated that secondary hyperparathyroidism due to hypocalcemic stress caused by excess fluoride ingestion disturbs normal metabolism of ground substance in calcified tissues of the body reflected as altered levels of the components of ground substance in the serum.