The combination effect of chemotherapy and cryosurgery on solid tumor have been evaluated using Ehrlich tumor implanted in hind-limbs of ddN mice. Following regimens were performed. 1) Mitomycin C (MMC) lmg/kg i.p. as a chemotherapeutic agent. 2) cryosurgery -60 degree C for 1.5 minutes. 3) various combination of MMC and cryosurgery. Each average life-span was A) without therapy: 23.8 +/- 4.3 days, B) MMC: 28.0 +/- 4.0 days, C) cryosurgery: 29.5 +/- 6.1 days. Combination therapy which cryosurgery was first performed and then MMC was administered was most effective among various combinations. And the life-span was significantly extended to 38.7 +/- 5.2 days compared with that of each single therapy. When PSK, a immunopotentiator, was added to this regimen, the life-span was extended to 45.0 +/- 9.3 days. The immunological aspects of these regimens were examined by radioisotopic foot-pad assay. Transient increase of cellular immunity was observed in cryosurgery group. The effect of cryosurgery on uptake of anti-tumor agent into tumor tissue were also studied using 3H-labelled 5FU and 14C-labelled 5FU. It was revealed that the uptake rate was significantly increased in tumor margin, but not in tumor center. When the uptake in tumor margin was examined at serial time after cryosurgery, peak of increased uptake was observed at 6 and 12 hours after cryosurgery. Satisfactory response was obtained in clinical application of cryochemotherapy based on these experimental findings.U