Changes in the concentrations of zinc (Zn) copper (Cu), cobalt (Co), and manganese (Mn) in wet soft tissues of 4–6 week old male and female New Zealand white rabbits administered increasing amounts of fluoride (F) were investigated. Four groups of six rabbits consisting of an equal number of individually housed males and females were given drinking water containing 0 (Group I, control), 50 (Group II), 100 (Group III), and 200 (Group IV) ?g NaF/mL. After 90 days the animals were sacrificed by anaesthesia with chloroform, and samples of liver, kidney, muscle, heart, and lung tissue were collected. Zn concentrations were significantly lower in liver, kidney, heart, and lung tissues in Group II than in the control Group I, but the lower level in muscle tissue was not significantly different from that of the control level. Cu concentrations, although lower in all five tissues of the Group II rabbits, differed significantly only in the muscle, heart, and lung tissues between the control Group I and the treatment Groups II, III, and IV. Co concentrations in all tissues in Group II were also significantly lower than in Group I, but in the other two Groups III and IV no definite pattern of change was evident. Mn concentrations in all the tissues of Group II were lower than in Group I and were significantly lower only in the liver, heart, and lung tissues of Group II but not in Groups III and IV. Although the levels of Zn, Cu, Co, and Mn declined with increasing F intake, the maximum decrease occurred in the lowest F-exposure Group II rabbits, suggesting a paradoxical F dose response relationship. A likely mechanism for these toxic effects is the interaction of these electropositive trace elements with F inside the gut tract and other body tissues. However, further studies are needed to elucidate exactly how these interactions occur.