The purpose of this study was to investigate the genotoxic effects of chronic fluoride exposure on mammalian cells in vivo by use of the mouse bone-marrow micronucleus test and the sperm morphology methodology. Mice of genotype B6C3F1 were obtained at weaning and maintained on a low-fluoride diet (less than 0.2 ppm F) ad libitum throughout the experiment. The animals were randomly assigned to seven groups and given fluoride (as sodium fluoride) in concentrations ranging from 1.0 to 75 ppm in the drinking water. Negative (distilled water) and positive (cyclophosphamide) controls were included. After a 21-week treatment period, the animals were killed by cervical dislocation, and blood was obtained by cardiac puncture. Slides of femur marrow cells were prepared and blindly examined for the frequency of micronucleated polychromatic erythrocytes (MN-PCE). Slides of sperm from the cauda epididymides of the male mice were also prepared and similarly examined for morphological abnormalities. Weight of the testes was recorded, and the plasma, humeri, testes, and carcasses were saved for fluoride analyses. Analyses of bone and plasma fluoride confirmed the effective absorption of fluoride following ingestion. The frequency of MN-PCE, the count of abnormal sperm, and the weight of the testes for mice chronically exposed to fluoride, in doses ranging from approximately 0.3 to 23 mg/kg/day, were not significantly different from those of the negative control animals. The results of this study support the view that fluoride has no genotoxic effects.