We have generated an optimized inducible recombination system for conditional gene targeting based on a Cre recombinase–steroid receptor fusion. This configuration allows efficient Cre‐mediated recombination in most organs of the mouse upon induction, without detectable background activity. An ES cell line, was established that carries the inducible recombinase and a loxP ‐flanked lacZ reporter gene. Out of this line, completely ES cell‐derived mice were efficiently produced through tetraploid blastocyst complementation, without the requirement of mouse breeding. Our findings provide a new concept allowing the generation of inducible mouse mutants within 6 months, as compared to 14 months using the current protocol.