Abstract: Objective To study the interaction of fluorine,calcium and iodine on 5-hydroxy tryptamine(5-HT) and learning-memory in rats.Methods Wistar rats were randomly divided into 8 groups based on 2?2?2 factorial design:moderate concentration of fluorine and high concentration of fluorine,moderate concentration of calcium and high concentration of calcium,moderate concentration of iodine and low concentration of iodine.After six months,the 5-HT,escape latency and exploring distance were measured.Results According to the results of factorial ANOVA,the significant interaction effects of calcium with iodine to 5-HT content in hippocampus were found(F=9.978,P=0.002).The contents of 5-HT in lower and moderate concentration of iodine group were 1006.3±537.6 and 1824.8±612.7 ng/g under moderate fluorine and high calcium,1132.0±365.9 and 1 548.2±476.7 ng/g under high fluorine and moderate calcium,1 085.7±508.7 and 1983.9±862.7 ng/g under high fluorine and high calcium,respectively.No significant interaction effect of calcium with iodine on escape latency was found(F=4.406,P=0.039).The significant interaction effect of fluorine,calcium and iodine on exploring distance was not found.Conclusion The significant interaction effects of fluorine,calcium and iodine on 5-HT content in hippocampus and escape latency are found.The interactions affect the learning-memory in rats.