We have examined the effect of hypoxia and nutrient depletion on the growth of human neuroblastoma cells with normal or enhanced expression of the N-myc oncogene, The combination of both conditions reduced the growth of neuroblastoma cells with normal N-myc expression, However, this effect was much more pronounced in neuroblastoma cells with enhanced N-myc expression and eventually resulted in apoptosis, presumably by the up-regulation of CD95, Our data suggest that therapeutic induction of tumor hypoxia and nutrient depletion (for example, by anti-angiogenesis) could help to improve the outcome of patients with neuroblastomas carrying the prognostically unfavourable N-myc amplification.