Cytotoxicity, minimal inhibitory concentrations of herpesviruses, and pharmacokinetic studies of cytosine arabinoside (ara-C) were done. Ara-C compared favorably with idoxuridine in in vitro studies of antiviral activity versus herpes simplex, varicella-zoster, and cytomegalovirus. However, ara-C was 10 times more toxic to tissue cultures, and concentrations in serum and urine of three patients who were given ara-C at acceptable dosages (1 mg/kg per day) were not measurable by our assay. These studies predict that ara-C is not likely to be a useful antiviral agent in humans because its therapeutic to toxic ratio approaches unity. These predictions of little clinical efficacy seem now to have been confirmed by clinical trails in humans. Pharmacokinetic studies outlined here should precede and help formulate controlled clinical trials of potential antiviral agents in humans.