Colorectal cancer represents one of the most important challenges in the field of cancer chemotherapy. 5-fluorouracil (5-FU) is used as the first-choice chemotherapeutic agent in the treatment of advanced gastrointestinal cancer. Despite this fact very little is known about the morphological changes of colon carcinoma after treatment with 5-FU. Thymusaplastic nude mice (n = 59) with subcutaneously heterotransplanted human coloncarcinoma (tubulo-papillary adenocarcinoma, grade II-III) were treated with 5-FU (40 mg/kg/body weight i. p. for five days). The animals were sacrificed, tumors were removed at 0 h, 24 h, 36 h, 48 h, 54 h, 60 h, 66 h, 72 h, 94 h, 118 h, 240 h after chemotherapy and the tumor tissue was embedded for light-microscopic and ultrastructural examination. Hydropic mitochondria and cytoplasmatic vacuoles were observed in tumor cells as early as 0 h after chemotherapy. These changes displayed a focal pattern. Damaged tumor tissue was surrounded by tumor cells with intact ultrastructure. In some regions tumor cells were separated from the basal membrane and showed signs of necrosis. These focal changes within the tumor tissue were observed from 0-240 h after treatment. Tumor capillaries did not show any damage. Treatment with 5-FU led to focal cytotoxic effects in the tumor. The remaining intact vascular system of the tumor may be a target for new therapy modalities.