Abstract. The responses of flexible bionetworks to extreme environmental changes were studied in several microorganisms. Gene and metabolic networks markedly changed with osmotic pressure in Saccharomyces cerevisiae. Even though large perturbations were observed in the gene network, the metabolic network changed moderately due to the limitation and constraints of redox and energy balances. A self organizing map (SOM) was a useful tool for analysis of massive amount of complex bionetwork data such as gene expression profiles. In the study on glutamate production by Corynebacterium glutamicum and Corynebacterium efficiens, it was concluded that there exists the most responsible enzyme to control of flux redistribution at a key branch point. Flux of biodegradable-polymer production pathway of Paracoccus denitrificans was well controlled by manipulating feeding speed of carbon sources. The heterogeneity of the population of the Escherichia coli cells in a continuous culture was studied...