The thyroid involvement is very significant feature of fluorosis due to fluoride accumulation in soft tissues. The participation of long term consumption of fluoride in drinking water on thyroid hormone status and deiodinating enzymes in fluorotic patients selected randomly from various parts of fluoride endemic areas, was elucidated. Type I (D1) activity was depressed significantly (P<0.001) in all fluorotic study groups in comparison to control, while type-II (D2) activity was lowered significantly (P<0.05) only in study group A-III (8.01-12.00 mg/L) and A-IV (12.01-16.00 mg/L). Serum TSH level was significantly (P<0.001) increased in fluoride exposed groups in comparison to control group whereas the level of rT3 showed a stepwise elevation with increase in water fluoride concentration. Decreased triiodothyronin (T3), thyroxine (T4), free T3 (FT3), free T4 (FT4) levels in serum were noted in all the fluorotic study groups (P<0.01) in comparison to the control. Pearson’s bivariate correlation analysis revealed significant (P<0.05-0.001) negative relationship between serum F vs D1 (r= -0.93); serum F vs D2 (r= -0.95); serum F vs T3 (r= -0.84) and serum F vs T4 (r = -0.87). There was direct correlation between serum F and rT3 (r = 0.84, P<0.004). Partial correlation analysis exhibited positive relationship between T3 and D1 (r= 0.96) and negative relationship between rT3 and D1. The regression coefficient of activity of D1 and serum F in all fluorotic paients revealed that water F being the strong predictor of involvement in depletion of D1 activity and increased levels of serum F. The lower activity of both D1 and D2 contribute to decrease in conversion of T4 toT3 and increased conversion of T4 to rT3. The depressed activity of D1 results in reduced conversion of rT3 into T2 and thereby allowing rT3 to accumulate in the body, resulting in hypothyroidism in fluoride intoxication.