Fluorosis may be identified in skeletal materials from ancient civilizations by macroscopic signs in teeth and bone and hard tissue fluoride levels. In the present study, human teeth, femoral, and rib specimens from the Van Fortress excavation, in Turkey, were examined for the presence of fluorosis. In addition, an animal study in rats was conducted as a model of human fluorosis, by examining the effects of fluoride administration, in various doses and for different durations, on weight loss, locomotor activity, fluoride accumulation, and deformation in bone and teeth. Fifty-six adult male Wistar albino rats, weighing 150-200 g, were divided into 7 different groups of 8 rats. Four acute groups were treated with 0 (control), 5, 15, and 50 mg/L of fluoride in drinking water for 7 days and three chronic groups were treated with 5, 15, and 50 mg/L of fluoride for 90 days. The results of the analysis of the human samples from the Van Fortress excavation showed that none of the dental, femoral, or rib samples had a fluoride content that was significantly greater than that of the surrounding soil. The results of the rat study showed that no significant differences between the groups were found in body weight on days 1, 30, 60, and 90. The rotarod locomotor test showed a significant (p<0.05) dose- and time-dependent reduction in locomotor activity as a result of the fluoride administration in the 50 mg/L chronic fluoride group compared to the control, 5 mg/L acute fluoride, 15 mg/L acute fluoride, and 5 mg/L chronic fluoride groups. Significant fluoride accumulation was found in the femoral neck (cortical tissue), the femoral head (trabecular tissue), and in rib bone. Light microscopy showed a severe thinning of the epiphyseal growth plate and bone trabeculae in the femoral bone tissue. We concluded that femoral bone (cortical and trabecular parts) and ribs are good sites for assessing the effects of fluoride exposure in animal models of human fluorosis.