The ability to generate tissue-specific ablation of gene expression has been extremely useful in connective tissue biology, as it can potentially overcome the early embryonic lethal phenotype often associated with universal gene knockout. The value of tissue-specific knockouts can be enhanced by also allowing gene ablation to occur at specific times during development, growth or aging. In the present work a transgenic mouse has been generated in which expression of Cre recombinase is under control of both the type II collagen promoter to allow cartilage-specific expression and a doxycycline response element to permit temporal control of expression. This mouse has been crossed with the Rosa26R reporter mouse, which possesses a floxed repressor element associated with a lacZ transgene, in order to validate the functional efficacy of the conditionally expressed Cre. The results demonstrate that excision of the floxed element can be achieved specifically in cartilage at different times during embryonic and juvenile development. The conditional Cre transgenic mouse should be a valuable tool to all interested in skeletal development.