In order to make clear whether the expression of biological activities and antitumor polysaccharides are under genetic control, the responses of mice to lentinan, a β-1,6;1,3-glucan, in the induction of several acute phase proteins (APPs) and T-cell-mediated vascular dilation and hemorrhage (VDH) were investigated. Twenty inbred strains of mice were divided into two groups according to their phenotypes in the induction of APPs when they were administered lentinan i.p. at a dose of 10 mg/kg; sensitive strains showed a marked increase in levels of APPs and resistant strains showed as low a level of APPs as non-treated control mice. No sex-related differences and no relation with H-2 haplotypes were found in the responses. Only low-level responses were observed in F 1 hybrid mice obtained by crosses between a sensitive and a resistant strain, indicating that the low APP response to lentinan is dominant. The N 2 progeny between the F 1 and a high responder segregated into high and low responders at a ratio of almost 1 : 1. These results suggest that a single major gene on an autosome is responsible for the induction of APPs. The induction of VDH also depended on the strains of mice. However, the strain distribution pattern of the VDH phenotype was distinct from that of the APP phenotype, indicating that the VDH-controlling gene was different from the APP-controlling gene. Further analyses with F 1 hybrid and backcross progeny mice suggested that the high VDH response was dominant, and that the phenotype was determined by a single major gene.