Streptococcus pneumoniae is a naturally transformable human pathogen. Genome and phylogenetic analyses uncovered two Spx-like global transcriptional regulators, SpxA1 and SpxA2, encoded by S. pneumoniae. spxA1 and spxA2 are not essential, but their simultaneous inactivation is lethal. SpxA1 represses transcription of the early competence operon comCDE and thereby negatively regulates the initiation of the X-state (competence). The molecular basis of this repression could be similar to that of SpxA of Bacillus subtilis, involving a specific interaction with the alpha subunit of RNA polymerase. S. pneumoniae lacks an SOS-like stress response and the X-state is proposed to be a general stress response mechanism in this species. In light of this, SpxA1-dependent repression could act to sense environmental or metabolic stresses and prevent launching of the X-state in the absence of stress.