A complete pathway (structures and energies of intermediates and transition state structures connecting them) from geranylgeranyl diphosphate to taxadiene, obtained using quantum chemical calculations, is described. This pathway is fully consistent with previous labeling experiments, despite differing in several subtle ways (in terms of conformations of certain carbocation intermediates and in the concertedness and synchronicity of certain bond-forming events) from previous mechanistic proposals. Also, on the basis of the theoretical results, it is proposed that the 2-fluoro-geranylgeranyl diphosphate substrate analogue in the recently reported X-ray crystal structure of taxadiene synthase is bound in a nonproductive orientation.