The anionic pyran copolymers represent a novel class of high molecular weight biological response modifiers with antitumor activity. Clinical pharmacology studies were performed on MVE-2, a polymer with an average molecular weight of 15.5 Kd. MVE-2 was analyzed in plasma and urine by HPLC. In addition, pharmacology studies were also performed using [14C] labeled MVE-2. The clearance of unlabeled MVE-2 from plasma was monophasic and the t1/2 for MVE-2 was extremely short (between 10 and 26 min). The apparent volume of distribution (Vd) varied from 12-18 l. Both the t1/2 and the Vd did not appear to be dose-dependent. The plasma clearance for [14C] labeled MVE-2 was studied in seven patients. The clearance of [14C] labeled MVE-2 fit a biphasic mathematical model. The alpha phase half-life was between 11 and 18 min while the beta phase half-life was between 70 and 85 min. Urinary excretion for either unlabeled drug or the [14C] label was between 30 and 45% of the administered dose. These studies show that, in man, the polyanionic macromolecule MVE-2 is cleared rapidly from plasma and excreted extensively in urine.