Coadministration of Tween 80 enhances the activity of adriamycin against selected experimental tumors in mice. Although some investigators have suggested a direct effect of Tween 80 on tumor cells, we wished to determine whether altered plasma concentrations of adriamycin occurred which might account for the apparent therapeutic synergism. Male CDF1 mice were treated i.p. with 6.7 mg/kg of adriamycin alone or combined with 5000 mg/kg of Tween 80 in physiologic saline. Fluorometric determination of adriamycin equivalents in plasma revealed significantly higher adriamycin concentrations 1 and 2 hr post treatment in mice that had received Tween 80. In three separate experiments, a significant, reversible increase in packed cell volume occurred in the peripheral blood of mice treated i.p. with Tween 80. This increase was maximal at 1-2 hr post treatment. The magnitude of the apparent plasma volume reduction accounted quantitatively for the increase in drug concentration. © 1981.