Neuroblastoma is a highly malignant neoplasm found in young children. Although children with high-risk neuroblastoma respond to chemotherapy, relapses are common. On account of poor treatment outcome, new treatment strategies are constantly sought for neuroblastoma. Polyamine analogues are potentially novel substances for treatment of neuroblastoma. In this study, we have treated two neuroblastoma cell lines, SH-SY5Y and LA-N-1, with the spermine analogue N1, N11-Diethylnorspermine (DENSPM). SH-SY5Y was the most sensitive cell line, in which DENSPM treatment resulted in an inhibition of cell proliferation and an induction of cell death. The cell death induced by DENSPM treatment was apoptotic, as evidenced by cleavage of procaspase 3 and induction of caspase-3 activity. In contrast, DENSPM treatment only resulted in a slight inhibition of cell proliferation in LA-N-1 cells. There were several possible causes for the lower sensitivity to DENSPM treatment in the latter cell line when compared with SH-SY5Y cells. DENSPM-induced polyamine depletion was more extensive in SH-SY5Y cells than in LA-N-1 cells. This was partly because of a higher induction of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase in the cell line SH-SY5Y. The DENSPM-induced polyamine depletion was also caused by the inhibition of ornithine decarboxylase. LA-N-1 cells contained a higher level of the prosurvival protein survivin, which was further increased after DENSPM treatment. In contrast, DENSPM treatment resulted in a decreased survivin level in SH-SY5Y cells.