Cyclin C was originally identified in a genetic screen for metazoan cDNAs that complement a triple knock-out of the CLN genes, involved in G1/S progression in S. cerevisiae. Unlike cyclin Ds and cyclin E, also identified in this screen, cyclin C has not been found to have a cell-cycle role in metazoa. Identified as the catalytic partner of cyclin C, Cdk8 is a novel protein-kinase of the Cdk family structurally related to the yeast Srb10 kinase. Cyclin C, Cdk8 and RNA polymerase II are found in a large multi-protein complex that shows structural as well as functional homologies with the yeast polymerase II holoenzyme. These observations and the sequence similarity to the kinase/cyclin pair Srb10/Srb11 in S. cerevisiae, suggest that cyclin C and Cdk8 control RNA polymerase II function.