Previous work on the transcriptional regulation of the mouse TNF-alpha promoter had indicated a major role for the NF-kappa B transcription factor in the induction of the gene by endotoxin. However, similar studies using the human promoter failed to establish a role for this factor. We measured the nuclear migration of NF-kappa B and the accumulation of TNF-alpha mRNA in murine T lymphoblasts and bone marrow-derived macrophages (BMDM) under different activation conditions, seeking to establish a correlation. Activation of NF-kappa B and accumulation of TNF-alpha mRNA correlated semiquantitatively under the following conditions: (1) inhibition of NF-kappa B by dithiocarbamates; (2) induction of TNF synthesis by taxol; (3) partial induction of TNF-alpha mRNA by various inducers in macrophages from lpsd mice; and (4) inhibition of NF-kappa B activation by a protease inhibitor. However, inhibition of TNF-alpha mRNA accumulation by cAMP inducers had no effect on NF-kappa B induction. We conclude that NF-kappa B translocation is necessary, but not sufficient for the transcriptional induction of the TNF-alpha gene by LPS in macrophages or by phorbol ester and ionomycin in T lymphocytes.