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Background: Air ions are molecules of air that have become ionized-that is, they have either lost or gained an electrical charge. Past speculation has suggested that exposure to positive air ions may be harmful to one's health, while exposure to negative air ions may be associated with beneficial health effects. Air ions arise from natural sources as well as direct-current transmission lines and commercial ionizers. Several recent clinical studies have suggested therapeutic effects of air ions on various types of depression at exposure levels 10- to 1000-fold higher than most previous human studies. The aim of this study was to assess the evidence from studies of laboratory animals for beneficial or adverse effects of air ions on health., Methods: Sixty-two studies (1935-2015) in nine topics areas were evaluated for quality and potential systematic bias by ARRIVE guidelines. Standardized mean differences or proportional differences between exposed and control groups were computed for 44 studies to quantitatively assess the strength of the evidence for exposure-related effects., Results: Many of the studies were conducted before 1990 and exhibited various reporting and methodological deficiencies, including small sample size, failure to control for the influence of potential confounding variables, lack of randomized assignment to treatment groups and blinded analyses, and statistical errors relating to treating group-exposed animals as individuals. The highest quality studies consistently reported no effects of exposure on any of the endpoints examined. There were no evident dose-response relationships within or across studies., Conclusions: Experimental studies of laboratory animals exposed to positive and negative air ions for minutes to years over a five-log unit range of intensities did not suggest any consistent or reliable effects on measures of behavior, learning and memory, neurotransmitters, tracheal function, respiratory infection, cardiovascular function, reproduction and growth, carcinogenesis, or other health endpoints. These data do not provide evidence of adverse or beneficial effects of air ion exposure on health, and did not suggest any biological mechanism of interaction, except perhaps for mechanosensory stimulation of body surfaces by static electric fields at high air ion concentrations.