We describe a chemosensitivity testing of head and neck tumors, in which a native-state histoculture, ie, a three-dimensional culture system that maintains important in vivo properties, including tissue architecture, was used. Fifteen specimens of head and neck tumors were evaluated for sensitivity to the following drugs: cisplatin (DDP) at concentrations of 1.5, 15, and 37.5 micrograms/mL; fluorouracil at concentrations of 4.0, 40, and 100 micrograms/mL; and combinations of cisplatin and fluorouracil in corresponding doses. Growth and measurement of drug responses were successfully completed in 10 specimens (five others were contaminated, four of them prior to instituting rigorous antibiotic washes). The results indicated cisplatin sensitivity in five of 10 patients; fluorouracil sensitivity in four of 10 patients; and fluorouracil-cisplatin sensitivity in seven of eight patients. Our preliminary results indicate that the native-state histoculture technique is feasible to test chemosensitivity of head and neck tumors.