Effect of electroporation (EP) in combination with a plant toxin, saporin, was studied using a human lung cancer cell line (PC9) and a pancreatic cancer cell line (ASPC-1). Target cells were electroporated in the presence of saporin and washed, and incubated for 72 hr. Proliferation inhibition in combination of EP and saporin was observed in parallel with the voltages and the saporin concentrations used. Proliferation of PC9 cells was completely inhibited at 1000 ng/ml of saporin in combination with EP (80-90 V, 10 ms, n = 8). High degree of proliferation inhibition was also obtained when ASPC-1 cells were electroporated in the presence of saporin (0.1-1000 ng/ml). PC9 or ASPC-1 tumor-bearing nude mice were treated with electroporation following the intratumoral injection of saporin (1 mg). Tumor necrosis was observed 24-48 hr after the combination therapy with saporin and EP. Six of nine mice with established PC 9 tumors and all the mice with established ASPC-1 tumors regressed completely 14 days and 6 days after the combination therapy, respectively.