Flavone acetic acid (FAA) is active against normally refractory murine sc tumors. Clinical studies are disappointing despite achievement of plasma profiles associated with the antitumor murine activity in man. To clarify the mechanism of action, we have followed histologic changes, tumor blood volume, and drug concentrations in a well-differentiated, slow-growing cystic adenocarcinoma in mice. FAA causes massive tumor necrosis beginning 2 hours after treatment. Tumor plasma volumes are reduced by 2 hours after treatment and tumor blood vessels are shutdown, which suggests that tumor vasculature plays a role in the dramatic response of sc tumors in pure-strain male NMRI mice.