The activated c-myc allele in Burkitt's lymphoma is associated with a clustering of somatic mutations within a discrete domain of intron I that define protein recognition sequences, designated as myc intron factors (MIF-1, MIF-2 and MIF-3). We have previously shown that MIF-1 binding activity consists of two polypeptides, myc intron binding polypeptide (MIBP1) and RFX1. In the present study we identified two polypeptides, p105 and p115, and showed that these proteins give rise to a DNA-protein complex at the MIF-2 as well as the adjacent MIF-1 site. In addition, we demonstrated that all four proteins interact with a novel MIF-1 like motif upstream from the c-myc promoter region, designated 5'MIF. These data suggest a model, where the interactions of MIBP1/RFX1 and p105/p115 with the MIF-like sites may play a role in the promoter topology of the c-myc gene.