Cytosine-arabinoside (ARA-C) effects on a new human neuroblastoma cell line (GI-ME-N), recently established in our laboratory, have been extensively tested. Low doses of ARA-C allowing virtually 100% cell viability induce morphological differentiation and growth inhibition; differentiated cells appear larger and flattened with elongated dendritic processes; such cells appeared within 48 hours after a dose of ARA-C as low as 0.1 microgram/ml. The new morphological aspect reached the maximum expression after 5-6 days of culture being independent of the addition of extra drug to the culture. A decrease in (3H)-thymidine incorporation was also observed within 48 hours being the cell growth completely inhibited at the 6th day. Membrane immunofluorescence with specific monoclonal antibodies showed several dramatic changes in NB-specific antigen expression after 5 days of treatment with ARA-C. These findings suggest that low ARA-C doses promote the differentiation of GI-ME-N neuroblastoma cells resulting in an altered expression of the malignant phenotype.