The tetracycline-controlled transactivation system is one of the most powerful tools for modifiable expression of exogenous genes. This system enables selective, stringent and quantitative regulation of transgenes in vitro and in vivo. By combining with antisense genes, ribozymes or genes encoding dominant negative mutants, it is also feasible to control certain endogenous gene functions. Combination with transgenic or 'gene knockout' technologies enables the generation of mice in which a certain gene function is conditionally reinforced or deleted. These sophisticated methods are useful for investigation of gene function during embryogenesis and in adult organs and for well-controlled gene therapy approaches. This article briefly outlines the concept of the tetracycline-regulated gene expression systems and addresses the current experience in kidney research.