Two different subpathways play a role in removal of UV-induced cyclobutane pyrimidine dimers (CPDs) by nucleotide excision repair (NER). The relatively slow global genome repair subpathway operates on all CPDs irrespective of their position in the DNA, whereas the transcription-coupled repair subpathway is responsible for the rapid removal of CPDs from transcribed strands. In Saccharomyces cerevisiae, the RAD26 gene is implicated in transcription-coupled repair. However, transcription-coupled repair is not completely absent in rad26 mutants, and therefore other gene products are possibly involved in this subpathway. Based on in vitro experiments with purified components, the transcription elongation factor S-II appeared to be a candidate for a function in transcription-coupled repair. To investigate a possible role of S-II in transcription-coupled repair in vivo in yeast, S-II null mutations were introduced into various genetic backgrounds differing in NER capacity. UV sensitivity was not altered by disruption of the S-II gene in a RAD+ (NER proficient) strain, or in rad26 (impaired in efficient transcription-coupled repair), rad7 (lacking global genome repair), or rad7 rad26 (lacking global genome repair, but having residual transcription-coupled repair capacity) mutants. Moreover, S-II did not influence the repair rate on the transcribed strand of the RPB2 gene, either in repair-proficient or in rad7 rad26 backgrounds. Hence, transcription-coupled repair is fully functional in yeast cells lacking the gene encoding S-II. Furthermore, S-II is not required for the Rad26-independent residual transcription-coupled repair in vivo.