Primary explant cultures of human neoplasms derived primarily from patients hav ing malignant lymphoma, melanoma, carcinoma, and tumors of the nervous system exhibited a wide range of morphological changes following exposure to graded doses of Vincaleukoblastine. Specific changes appeared to be associated with low, medium, and high dose levels, and progressive changes were observed following prolonged expo sure at each level. The over-all morphological change at the subtoxic dose levels was characterized by the alteration of pleomorphic multipolar elongated cells to an epithelial-like cell type. Progressive changes were characterized primarily by the loss of cytoplasmic material. In several cultures regeneration of the cytoplasm was observed 5-11 days following withdrawal of the drug at the medium and low dose levels. Metaphase arrest observed in vivoand in vitro by several investigators was also seen in these primary cultures. A fourto eightfold increase in the number of metaphases was found at the medium dose levels. The appearance of many multinucleated cells was one of the distinguishing features of the low dose levels. Several cells contained numerous small nuclei, and intermediary stages of nuclear cleavage and blebbing were frequently observed.