Biofilm formation on solid surfaces is a very common phenomenon among bacteria with important economic and medical consequences. A strain of Escherichia coli K-12 able to form a thick biofilm on inert surfaces such as glass or polystyrene has previously been isolated from a continuous culture in minimal media . Increased adhesion to solid surfaces by this mutant is the result of the overproduction of curli, a particular class of pili. A single point mutation resulting in the replacement of a leucine by an arginine residue at position 43 in the OmpR protein is responsible for this phenotype. The presence of the ompR234 allele significantly increases the expression of the curlin encoding csgA gene. Loss of adherence properties of several strains of adherent E. coli is caused by transduction of knockout mutations in either the csgA or ompR gene . Curli are therefore essential for biofilm formation and the EnvZ-OmpR two-component system regulates the synthesis of curlin, their major component. A similar regulation was demonstrated in Salmonella[2,3]. Besides osmolarity, curli expression in Salmonella and E. coli strains, including K12, avian E. coli and different clinical types, is highly regulated by environmental conditions such as temperature and the growth phase. Biogenesis of curli is restricted to temperatures below 30°C and the stationary growth phase [3–6]. Thus, it appears that curli production is tightly regulated by complex environmental signals and we used a genetic approach to characterize new systems at the molecular level required for biofilm formation on inert surfaces. Our results allow us to identify the Cpx signal transduction pathway as an important partner in the adherence process beside the EnvZ-OmpR pathway.