We have previously reported that L-4-oxalysine, a natural product in China, exhibits marked antitumor and immunoregulatory activities. The present study was set up to investigate the effect of L-4-oxalysine on the immunological activity of alpha-fetoprotein. It was observed in in vitro experiments that concanavalin A reactivity, one-way mixed lymphocyte reaction and interleukin-6 activity of spleen cells from hepatoma-22-bearing mice were significantly inhibited by various concentrations of alpha-fetoprotein. However, L-4-oxalysine functionally antagonized the alpha-fetoprotein-induced suppression of the mitogen- and one-way mixed lymphocyte culture-induced proliferation of spleen lymphocytes and interleukin-6 production by these cells in mice bearing the hepatoma-22 tumor. The results indicate that L-4-oxalysine has immunostimulatory activity and this effect of the agent counteracts the immunosuppression induced by alpha-fetoprotein, although L-4-oxalysine does not directly antagonize alpha-fetoprotein.