The effects of lentinan, an antitumor polysaccharide, on vascular reactions against vasoactive mediators were investigated in murine systems. Lentinan augmented intradermal reactions against bradykinin. Induction of acute phase proteins (APP) and the vascular dilatation hemorrhage (VDH) reaction on the ears have been reported to reflect the host responses to lentinan. The strain difference in the intensity of skin reactions coincided with those observed in VDH responses and with lentinan-induced antitumor effects against Sarcoma 180. Augmentation of skin reactions was not observed in T-cell-deficient mice. Inhibitors of lipoxygenase, thrombin and plasmin which reduced skin reactions also decreased the incidence of tumor necrosis positive mice among FBL-3-bearing mice treated with lentinan. Furthermore, B10D2 mice treated with fluorouracl (5-FU) and lentinan 10 days after S908.D2 transplantation showed complete tumor regression and augmented skin reactions, whereas augmentation of skin reactions and tumor regression were not observed in mice treated with 5-FU and lentinan 32 days after tumor inoculation. Taken together, these results suggest that these vascular reactions might play crucial roles in antitumor effects of lentinan and that the skin reaction, the convenient method for investigating vascular reactions, is a promising tool to monitor host sensitivity to lentinan in antitumor responses.