Dolastatin 15 1(4S,7S) is a potent cytostatic depsipeptide of marine origin. Analysis of the effects of the stereochemistry in the non-peptide moiety on activity revealed that chirality inversion in the aromatic terminal region preserves the antiproliferative activity. Dolastatin 15 1(4S,7S) is a cytostatic depsipeptide isolated from the marine molusc Dolabella auricularia. Its linear structure is related to that of dolastatin 10, another potent antineoplastic metabolite of the same origin. Detailed biochemical analysis has revealed a qualitatively similar activity profile for both agents, although dolastatin 10 presents higher potency in most studies. These agents are antimitotic and specifically interact with tubulin. Their cell cycle phase selectivity was confirmed by typical G2/M metaphase arrest analysis. The recent development of synthetic procedures for the preparation of dolastatin 10 was accompanied by a preliminary structure-activity analysis. Surprisingly, no such analysis has been performed on dolastatin 15. Having developed an efficient synthesis of dolastatin 15 we evaluate here the stereoisomerical requirements of the two chiral centers C-4 and C-7 present in the non-peptide moiety of the molecule on its cytotoxic activity.