The GAL11 gene encodes a transcription factor that is a component of the SRB/Mediator sub-complex of the RNA polymerase II holoenzyme in the yeast Saccharomyces cerevisiae. In agreement with this biochemical characterization, Gal11p has been found to be required for optimal production of mRNA from many yeast promoters, and recessive mutations in GAL11 have been shown to cause pleiotropic defects. Despite this progress, the role of Gal11p in gene regulation remains largely unknown. In a multicopy suppressor analysis of a gal11delta mutation we have identified genes encoding proteins that are part of, or can interact with, the RNA polymerase II transcription complex, as well as factors involved in cell cycle regulation. Among the suppressors that are clearly related to the transcriptional apparatus, Gal11p genetically interacts with components of the SRB/Mediator complex, as well as with factors such as TFIIE and TFIIH that are required for promoter clearance and transcription elongation by RNA polymerase II. These findings, taken together with published results of biochemical and genetic analyses, suggest a role for Galllp at the interface between the SRB/Mediator complex and the general transcription factors TFIIE and TFIIH, which modulate, via phosphorylation of the CTD, the activity of the RNA polymerase II during the transition between initiation and elongation.