Taxol cytotoxicity was evaluated in human head and neck squamous carcinoma cell lines growing as multicellular tumor spheroids (MTS) and compared with monolayered culture using conventional clonogenic assays. End points were respectively the concentration inhibiting 50% of the cellular growth (IC50) in clonogenic assays and the concentration required to induce a 50% decrease in the MTS volume (ID50) or number in the overall spheroid population (SCC50). A significant difference was observed when the cells were exposed for 10 days to Taxol as a consequence of the different growth kinetics of the spheroids. After 16 day exposure of spheroids to Taxol, no difference remained between ID50 and IC50. In addition, a significant correlation was found between individual spheroid sensitivity to Taxol (ID50) and the spheroid population sensitivity (SCC50). Both parameters (ID50 and SCC50) defined in cell models appear useful for the evaluation of chemosensitivity of three-dimensional structures known to be closer to in vivo tumor models.