We have developed a novel in vivo model of human small-cell lung carcinoma (SCLC) using orthotopic reconstitution by injecting human SCLC in the tail vein of severe combined immunodeficient (SCID) mice whereby the SCLC grows in the lung and other organs. Cisplatin (DDP) had significant antitumor effects on the SCLC growing orthotopically in the lung whereas mitomycin C (MMC) did not, thereby reflecting the clinical situation. However, the opposite effects were found when the SCLC was growing subcutaneously, where the tumors responded to MMC and not to DDP. This suggests that the tumors growing orthotopically reflect the clinical effects of drugs on human SCLC more closely than the tumors growing subcutaneously. Therefore, this orthotopic reconstitution model of human SCLC in SCID mice is thought to be useful for studies on the treatment of human SCLC and emphasizes the need for orthotopic models for relevant cancer drug evaluation.