Pseudomonas aeruginosa mutants that overproduce the exopolysaccharide alginate and assume mucoid phenotype are associated with the establishment of chronic respiratory disease in cystic fibrosis. The initially invading strains are nonmucoid and frequently convert into the mucoid form. Mucoidy is regulated at the transcriptional level, mainly at the promoter of the algD gene. Control of the algD promoter represents a cooperative effort of several types of regulatory elements including bacterial signal transduction factors (principally through the response regulator AlgR) and histone like elements (e.g., Hp1 and possibly IHF). Our more recent studies have shown that conversion to mucoidy is a result of mutations in the muc genes within the algU-mucA-mucB cluster. The algU gene encodes a protein that resembles Spo0H, a sigma factor from Bacillus subtilis, which controls development of sporulation and competence. The mucA and mucB genes appear to control the activity of AlgU. Frameshift mutations that inactivate these proteins result in a strong transcriptional activation of algD, and conversion to mucoidy in both laboratory and clinical strains of P. aeruginosa.