We reported previously that the v-rel protein (p59v-rel) exists in a high molecular weight complex with at least four other proteins in the cytoplasm of v-rel-transformed chicken pre-B lymphoid cells (Simek, S. & Rice, N.R., J. Virol., 62, 4730-4736, 1989). One of these proteins is the chicken c-rel protein, but the identities of the others (of about 36 kDa, 115 kDa, and 124 kDa) are unknown. In this report we extend that observation to additional v-rel-transformed cell lines of both pre-B and B cell phenotypes. We also introduced and expressed v-rel in several other avian cell lines (a chicken T cell line, chick embryo fibroblasts, and quail fibroblasts) and found that in these cells p59v-rel was complexed with the same proteins as observed in the v-rel-transformed cells. Thus, the associated proteins are not limited to pre-B cells, but occur and complex with p59v-rel in B cells, T cells, and fibroblasts. We next examined five uninfected avian cells and tissues and found that, with only one exception, p75c-rel was complexed with p36, p115, and p124. Thus, in most cases complex formation is not limited to or dependent on the presence of the transforming v-rel protein, but also occurs with the normal c-rel protein. To determine whether a mammalian c-rel protein is similarly associated with other proteins, we screened murine cell lines for the presence of c-rel mRNA. In agreement with our earlier findings, we found the highest expression in mature B cells, although several pre-B and myeloid cell lines were also strongly positive. Using one of the B cell lines, we detected the murine c-rel protein. We found that, like its avian counterpart, it is a protein of about 75 kDa and is associated with proteins of 36 kDa and 115 kDa. Sephacryl S-400 chromatography revealed that both the avian and murine complexes are of high molecular weight, with an average size of about 400 kDa.