A series of 4''-dehydrated derivatives of various dimeric Vinca alkaloids was synthesized to further define the structure-activity relationships of Vinca alkaloids with oncolytic potency. The concentrated H2SO4 dehydration in most cases gave mixtures of the 3'',4''- and 2 isomeric 4'',20''-alkenes, which were isolated and characterized primarily by proton and 13C NMR. Compounds tested for antitumor activity include the 3 dehydro isomers of 4-deacetylvinblastine, 4-deacetylvincristine and 4-deacetylvinblastine-23-amide and some 4''-dehydrated derivatives epimeric at C-18''. Generally, the decrease in toxicity impaired by the new double bond was accompanied by a decrease in potency. An exception was 3'',4''-dehydro-4-deacetylvincristine, which showed a decrease in toxicity and increase in potency against at least 1 tumor in which vincristine itself has little effect.