This study was designed to quantitate and compare the major features of the short-term pharmacokinetics of fluoride–i.e., the plasma (Cp), renal (Cr), and extra-renal (Cer) clearances–in young adult dogs, cats, rabbits, rats, and hamsters. Plasma and urine samples were collected for seven h after the iv administration of fluoride (0.5 mg F/kg). Cp ranged from 3.5 to 8.6 mL/min/kg in the dog and hamster, respectively. Cr ranged from less than 1.5 mL/min/kg in the dog and rabbit to about 3.5 mL/min/kg in the rat and hamster. Cer ranged from 2.1 mL/min/kg in the dog to over 4.5 mL/min/kg in the cat, rabbit, and hamster. It was concluded that (1) there are major quantitative differences in the metabolic handling of fluoride among the five species, and that (2) Cp, Cr, and Cer values of the young adult dog, when factored for body weight, resemble those of the young adult human most closely.