Interferon regulatory factor-4 (IRF-4) is a lymphoid-specific transcription factor that plays crucial roles in the development and the functions of immune cells. B lymphocytes express IRF-4 constitutively. In this report, we investigated the transcriptional control of IRF-4 in B lymphocytes. Successive deletions of the IRF-4 promoter from -4799 revealed that the region between -51 and -28 (5'-CGCCCGCCCCAGGCCCCGCCCCA-3') was required for the basal promoter activity. Mutations in the distal and proximal sites of this GC-rich sequence resulted in 62 and 81% reductions in the IRF-4 promoter activity, respectively. EMSA observations revealed the formation of a protein complex with the corresponding DNA, which was sensitive to mutations in the GC-rich sequences. UV photocrosslinking assays identified a novel 60 kDa protein with a similar sequence preference. The possible involvement of this factor in the regulation of IRF-4 gene expression is discussed.