Water-soluble fullerenes have recently been shown to exhibit considerable in vitro biological activity including cytotoxicity, site-selective DNA cleavage and inhibition of HIV protease. To assess the potential of these compounds as drugs, studies on the in oiuo behavior of fullerenes are needed. We therefore set out to synthesize a radiolabeled, water-soluble fuIIerene, in order to obtain data on the oral absorption, distribution and excretion of this class of compounds. We synthesized a 14C-labeled water-soluble [60] fuIIerene using dipolar trimethylenemethane, which undergoes cycloaddition to [60] fXIerene. When adrninistered orally to rats, this compound was not efficiently absorbed and was excreted primarily in the feces. When injected intravenously, however, it was distributed rapidly to various tissues, and most of the material was retained in the body after one week. The compound was also able to penetrate the blood-brain barrier. Acute toxicity of the water-miscible lllerene was found to be quite low. Although the water-soluble fuIIerenes (and possibly their simple metabolites) are not acutely toxic, they are retained in the body for long periods, raising conterns about chronic toxic effects. The fact that fullerenes distribute rapidly to many tissues suggests that they may eventually be useful to deliver highly polar drugs through membranes to a target tissue, however, and they may even have applications in the delivery of drugs to the brain. Recent advances in fnllerene synthetic chemistry may also make it possible to control fnllerene absorption/excretion profiles in the future.