Enhancement of specific transplantation resistance to a syngeneic tumor (KMT-17) was observed in WKA rats treated with the antileukemia drug busulfan (BU) (15 or 8 mg/kg) 5 days after immunization with X-irradiated KMT-17 cells. Similar enhancement was also produced by treatment with mitomycin C (1 mg/kg), but not cyclophosphamide (40 or 20 mg/kg), adriamycin (3 mg/kg), or BU (4 mg/kg). The therapeutic effect of BU on transplanted KMT-17 tumor in WKA rats was relatively weak, but the therapeutic efficacy of BU as an immunomodulator appeared to be almost equal to that of PS-K, lentinan, or neurotropin. By means of the tumor-neutralizing assay using spleen cells, a stronger antitumor immune response was observed in BU-treated tumor-bearing rats than in the BU-untreated control group. An improvement of the therapeutic effect was obtained by combining neurotropin with BU, although its monotherapeutic effect was insufficient.