Epothilones A and B, two compounds that have been recently isolated(1) from myxobacterium Sorangium cellulosum strain 90, have generated intense interest(2-16) among chemists, biologists and clinicians erring to the structural complexity, unusual mechanism of interaction with microtubules and anticancer potential of these molecules. Like taxol* (refs 17, 18), they exhibit cytotoxicity against tumour cells by inducing microtubule assembly and stabilization(3,4), even in taxol-resistant cell lines. Following the structural elucidation of these molecules by X-ray crystallography in 1996(1), several syntheses of epothilones A (refs 12-16) and B (ref. 19) have been reported, indicative of the potential importance of these molecules in the cancer field. Here we report the first solid-phase synthesis of epothilone A, the total synthesis of epothilone B, and the generation of a small epothilone library. The solid-phase synthesis applied here to epothilone A could open up new possibilities in natural-product synthesis and, together with solution-phase synthesis of other epothilones, paves the way for the generation of large combinatorial libraries of these important molecules for biological screening.