Histological serial sections of resection specimens from 37 patients suffering from advanced squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx, and supraglottic region of the larynx were examined after pre-operative chemotherapy with methotrexate (M), bleomycin (B), and cisplatin (P) - (MBP). Pathohistological grading criteria for SCC from various sources were used. Results were compared with initial biopsy specimens. Statistical interpretation was carried out with the sign test. Mode of growth, degree of keratinization, mode of invasion and cellular reaction showed a significant change towards more benign behaviour. However, the maturity of the remaining tumour cells showed a considerable tendency towards greater malignancy. Some grading criteria proved to be insufficient for the determination of statistically significant alterations, with the exception of keratinization, which showed a change towards benignity. Results obtained for the different mechanisms of action of drugs used in the MBP-combination and the different regression behaviour of variously differentiated squamous cell carcinomas under chemotherapy are discussed in this study.