OBJECTIVE: Investigating the influence of combined iodine and fluoride on phospholipid and fatty acid composition in brain cells of rats. METHODS: Five groups of rats were provided with deionized drinking water containing 0 and 150 mg/L NaF, and containing both 150 mg/L NaF and 0.003, 0.03 or 3 mg/L KI respectively for 5 months. Then phospholipid and fatty acid composition were determined using liquid chromatography. RESULTS: The phospholipid composition had no obvious change. The high concentration fluoride (150 mg/L) and high concentration Iodine (3 mg/L) with high concentration fluoride could cause significant changes of the fatty acid composition in brain cells of rats, the proportion of unsaturated fatty acid (C18:2) was significantly decreased and the saturated fatty acid (C12:0) increased obviously. The antagonistic action of 0.03 mg/L KI drinking water on this kind of influence induced by 150 mg/L NaF was the most evident, whereas that of 3 mg/L KI was action of synergetic toxicity. CONCLUSION: Fluorosis had obvious influence on phospholipid and fatty acid composition in brain cells of rats, and its mechanism might be associated with action of lipid peroxidation, and 0.03 mg/L KI is the optimal concentration for the antagonistic action with this influence from fluorosis.