Mutations in the S. cerevisiae SPT15 gene were isolated as suppressors of insertion mutations that alter the transcription of adjacent genes. Molecular and genetic analysis of the cloned SPT15 gene has shown that it is the same as the gene that encodes the TATA binding factor TFIID. Analysis of spt15 mutants has demonstrated that alterations in TFIID can change transcription initiation in vivo. In addition, we demonstrate that TFIID is essential for growth and that spt15 mutations are pleiotropic, as spt15 mutants grow slowly and have defects in both mating and sporulation. Therefore, TFIID is an essential transcription factor in vivo, likely to be required for normal expression of a large number of genes.