The proliferation of eukaryotic cells is controlled at specific points in the cell cycle, particularly at the G1 to S and the G2 to M transitions. It is well established that the Cdc2 p34-cyclin B protein kinase plays a critical role in the G2 to M transition while cyclin A associates with Cdk2 p33 and functions in S phase. Considerable effort directed towards the identification of G1 cyclins has led to the isolation of cyclin D, cyclin C and cyclin E. Of these, cyclin D corresponds to a putative human oncogene, designated PRAD1, which maps at the site of the Bcl1 rearrangement in certain lymphomas and leukemias. Two additional human type D cyclins, as well as their mouse homologs, have been identified. Evidence has established that members of the cyclin D family function to regulate phosphorylation of the retinoblastoma gene product, thereby activating E2F transcription factors.