Organ formation requires spatio-temporal proliferation and differentiation of precursor cells. During lens development, placodal cells in the posterior lens vesicle exit from the cell cycle and enter into the process of differentiation. Cyclin-dependent kinase inhibitors play critical roles in cell cycle exit and promote differentiation in several tissues. We have found that p27kip1 is expressed in the posterior lens cells that undergo differentiation to form the differentiated fiber cells. The transcription factor L-Maf is expressed in these cells earlier than p27kip1. From in ovo gain- or loss-of-function experiments, we have found that L-Maf can, respectively, induce or inhibit the expression of p27kip1 in lens cells. Promoter assays using the 5' upstream sequences of the human p27kip1 gene indicate that L-Maf can activate p27kip1 transcription through the basal regulatory region. We suggest that L-Maf regulates cell cycle exit of the posterior lens cells by activating p27kip1, and thus directs fiber cell differentiation during lens formation in chick.