Background: Previous systematic reviews of epidemiology studies have found support for a geographical association between high levels of naturally occurring fluoride in water (>1.5 ppm) and lower IQ in children. Most of the evidence from humans is from fluoride-endemic regions having higher background levels of fluoride compared to the fluoride concentrations historically used in community water fluoridation programs (0.7-1.2 ppm). Confidence in this body of evidence is limited, primarily due to poor reporting quality, lack of consideration of confounding (e.g., nutritional status, socioeconomic status, iodine deficiency), and concern for co-exposures to relatively high levels of other known neurotoxicants such as lead or arsenic. A systematic review of experimental animal studies could help in interpreting the human evidence. Objective: To investigate whether fluoride exposure has detrimental impacts on neurobehavior in laboratory animal studies, prioritizing assessment of learning and memory outcomes. Confidence in the body of evidence was assessed according to one of four statements: (1) High, (2) Moderate, (3) Low, or (4) Very Low/No Evidence Available. Methods: We included experimental animal studies that used mammalian species (whole organism) exposed during development or adulthood, which compared the effects of oral exposure to various fluoride concentrations to vehicle controls on neurobehavioral responses. The principal outcomes were learning and memory, but other neurobehavioral studies were included (e.g., anxiety, motor activity, aggression, sexual behavior). Studies assessing brainrelated cellular, morphometric or histological endpoints were considered beyond the scope of this analysis. A literature search was performed up to January 14, 2016, using PubMed, BIOSIS, EMBASE, Scopus, Web of Science, PsycINFO, and several specialized databases. There were no date or language restrictions, and unpublished data and abstracts were excluded. Risk of bias was assessed regarding randomization, allocation concealment, blinding, exposure characterization, health outcome assessment, incomplete outcome data, selective outcome reporting, and other biases. Results: The database searches yielded 4,643 unique records and 13 records were identified from other sources. Of the 4,656 studies, we identified 68 studies using mice or rats and testing drinking water or dietary concentrations of 0.45 to 272 ppm fluoride (0.12 to 40 mg/kg-d). Most included studies were published after 2000. Forty-eight studies addressed learning and memory, 16 of which assessed exposure during development.