This thesis documents the author's research on the pathogenesis and epidemiology of the pseudomonads in particular the association of Pseudomonas aeruginosa and Pseudomonas cepacia with pulmonary colonisation and progressive lung damage in patients with cystic fibrosis. One of the key virulence determinants in pulmonary colonisation of cystic fibrosis patients by P. aeluginosa is biosynthesis of alginate. This unusual bacterial polysaccharide confers a strikingly mucoid colonial phenotype and in vivo is associated with the formation of microbial biofilms. During the last two decades, my research has focused on the genetic and molecular regulation of alginate biosynthesis. The origins of these studies derive from my PhD research on pyocins which led to the development of an internationally recognised typing system for P. aeruginosa. In the early 1970s, pyocin typing data suggested that mucoid P. aeruginosa arise in vivo, by mutation or environmental stimulation following primary asymptomatic colonisation with a nonmucoid parent strain. My genetic studies of alginate regulation were developed in the mid 1970s during an MRC Travelling Fellowship at Monash University, Melbourne and produced the first evidence for chromosomal genes controlling the mucoid phenotype. These embryonic studies and the muc mutations which were identified were to play an important part in the subsequent molecular unravelling of the sensory regulation of alginate biosynthesis in collaboration with colleagues in San Antonio. From 1980, my research on the microbiology of pulmonary infections in cystic fibrosis patients has included studies of antibiotic therapy, the epidemiology of pseudomonads and the use of animal models of chronic respiratory infection. Currently, in collaboration with colleagues at the MRC Human Genetics Unit in Edinburgh, I am involved in microbiological studies of the newly developed cystic fibrosis mouse. The most common microbial pathogens in cystic fibrosis patients are Staphylococcus aureus, Haemophilus influenzae and P. aeruginosa. From the mid 1980s, however, transmissible and potentially fatal pulmonary infection by the phytopathogen P. cepacia has caused increasing concern to patients and those involved in patient care. A major aim of my current research is to clarify the epidemiology of P. cepacia and to identify the host and bacterial factors associated with transmission and pathogenesis.