The 5' flanking region of the mouse muscle creatine kinase (MCK) gene contains two repeat sequences-a mononucleotide repeat, (A)(22) (-2694 to -2673), and a tetranucleotide repeat, (GTTT)(8) (-2962 to -2931). We show here that these repeats in the mouse MCK gene bind to specific nuclear protein factors. Some of the factors interacting with these sequences are tissue-specific and show age-related decrease in the binding activity. Nonspecific competitor and heterologous DNA probes failed to compete out the complexes showing that the interaction is specific to the repeat sequences. These proteins may have a role in the expression of the gene during aging.