A comparison of the pharmacokinetics of the trace element cobalt and the protoporphyrin chelate of this metal, cobalt-protoporphyrin, was conducted in male Sprague-Dawley rats. Following subcutaneous treatment (250 mumol/kg body weight), cobalt was found predominantly (>95%) in plasma, from which it was rapidly eliminated (t1/2 almost-equal-to 25 hr). Cobalt-protoporphyrin, also found almost exclusively in plasma (>95%), exhibited a much slower elimination rate (almost-equal-to 3 days) in comparison to the noncomplexed metal. Four weeks after dosing with either inorganic cobalt or cobalt-protoporphyrin, tissue levels of cobalt were measured by graphite furnace atomic absorption spectroscopy. The kidney retained the highest levels of cobalt (1 and 4 mug/g dry tissue weight, respectively), although in cobalt-protoporphyrin-treated rats, elevated levels of cobalt (1.5 mug/g) were still observed in the spleen, gonads, lung, and thymus up to 4 weeks posttreatment. These differences in pharmacokinetics between inorganic cobalt and cobalt-protoporphyrin are discussed in terms of the differing biological properties exhibited by the metal in its different chemical associations.