Studies of NF-κB suggest that this enhancer binding activity corresponds to a family of at least four proteins (p50, p55, p75, and p85) differentially induced with biphasic kinetics during T cell activation. While p55 and p50 are closely related to the 50 kd DNA binding subunit of NF-κB, p75 and p85 exhibit DNA binding properties that distinguish them from this 50 kd poly-peptide and its regulatory subunits IκB and p65. All four members of this κB-specific protein family are structurally related to the v-Rel oncoprotein and one, p85, appears identical to human c-Rel. v-Rel, but not nontransforming v-Rel mutants, binds to the κB enhancer and inhibits NF-κB-activated transcription from the IL-2 receptor α promoter and HIV-1 LTR. These findings suggest a Rel-related family of κB enhancer binding proteins and raise the possibility that the transforming activity of v-Rel is Iinked to its inhibitory action on cellular genes under NF-κB control.