Dental fluorosis (DF) affects the appearance and structure of tooth enamel and can occur following ingestion of excess fluoride during critical periods of amelogenesis. This tooth malformation may, depending on its severity, influence enamel and dentin microhardness and dentin mineralization. Poor correlation between tooth fluoride (F) concentration and DF severity was shown in some studies, but even when a correlation was present, tooth fluoride concentration explained very little of DF severity. This fact calls into question the generally accepted hypothesis that the main factor responsible for DF severity is tooth fluoride concentration. It has been shown previously that genetic factors (susceptibility to DF) play an important role in DF severity although DF severity relates to individual susceptibility to fluoride exposure (genetics), tooth fluoride concentration relates to fluoride ingestion (environmental). The objective of this study was to investigate the correlation between tooth fluoride concentration, DF severity, and tooth mechanical and materials properties. Three strains of mice (previously shown to have different susceptibility to DF) at weaning were treated with four different levels of F in their water (0, 25, 50, and 100 ppm) for 6 weeks. Mice teeth were tested for fluoride by instrumental neutron activation analysis (INAA), DF severity determined by quantitative light-induced fluorescence [QLF], and tooth quality (enamel and dentin microhardness and dentin mineralization). Tooth fluoride concentration (environment factor) correlated positively with DF severity (QLF) (rs=0.608), fluoride treatment group (rs=0.952). However, tooth fluoride concentration correlated negatively with enamel microhardness (rs=-0.587), dentin microhardness (rs=-0.268) and dentin mineralization (rs=-0.245). Dental fluorosis (genetic factor) severity (QLF) correlated positively with fluoride treatment (rs=0.608) and tooth fluoride concentration (rs=0.583). DF severity correlated negatively with enamel microhardness (rs=-0.564) and dentin microhardness (rs=-0.356). Genetic factors (DF severity) and the environmental factor (fluoride concentration in tooth structure) have similar influence on tooth biomechanical properties, whereas only the environmental factor has an influence on tooth material property (mineralization).