Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2 alpha of 11.1 +/- 4 min and a t1/2 beta of 246 +/- 78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7 +/- 12 and 718 +/- 149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5 +/- 1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg X min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity.