The NF-kappa B/Rel family is a growing class of transcriptional regulators whose members share the conserved Rel-homology domain, involved in specific DNA binding and dimerization. They interact with the regulatory elements of many different genes and are involved in the regulation of lymphoid-specific and inducible transcription. We tested whether these factors could alone activate a gene in transgenic mice. We report here that a minimal promoter containing three copies of a binding site for these proteins allows tissue-specific and inducible transgene activation. In lymphoid tissues constitutive transgene expression correlates with the presence of a constitutively active p50/RelB heterodimer. Other organs that only contain the p50 homodimer do not express the transgene. In contrast to this constitutive activity mediated by p50/RelB, the p50/p65 heterodimer (which is NF-kappa B) could confer inducible transgene activation in embryo fibroblasts. Thus two different members of the NF-kappa B/Rel family of transcriptional activators are involved in tissue-specific and inducible gene activation in transgenic mice.