Rel/NF-kappa B transcription factors play fundamental roles in the immune system. These structurally-related proteins share common pathways of activation that involve their release from inhibitory I kappa B factors in response to stimuli. Accumulating evidence also points to a role for Rel and I kappa B proteins in cellular growth control and oncogenesis. The rearrangement and amplification of genes encoding Rel/NF-kappa B and I kappa B proteins in several human cancers, together with the acute oncogenicity of the retroviral v-rel oncogene in birds and mammals, suggests a correlation between their effects on gene expression and their role in malignancy. This review focuses on the current status of the association of Rel/NF-kappa B and I kappa B proteins with neoplastic cell transformation in vitro and in vivo.