We studied the effect of lentinan, a fungal polysaccharide immunomodulator, on mouse peritoneal macrophages. The i.p. treatment of mice with 10 mg/kg lentinan affected the number, plastic-adherence, and endogen peroxidase activity of peritoneal cells. The cytotoxicity of lentinan-stimulated peritoneal macrophages was determined against several murine and human metastatic tumor targets: Lewis lung carcinoma (LLT) and two human melanomas, and was found to be significantly higher than that of the macrophages from control animals. However, the highly metastatic variant of LLT (LLT-HH) was resistant to the cytolytic effect of resident and lentinan-activated macrophages as well, indicating that the stimulation for cytotoxicity depends not only on the functional activity of the effector but also on the sensitivity of the target.