The Hox family of transcription factors are expressed at different domains along the rostrocaudal (R-C) body axis during development. To examine the function of Hoxc8 and Hoxc9 in specific cell types and at different developmental times, we have generated and characterized loxP flanked (floxed) Hoxc8 and Hoxc8→Hoxc9 replacement alleles of mice, with either GFP or LacZ reporters. Although all four alleles of mice behave like wild-type controls in motor behavioral testing, slight differences in endogenous Hox gene expression were observed among these alleles depending on the type of reporters used and the presence of Hoxc9 cDNA in the targeting constructs. The efficiency of Cre-mediated recombination was evaluated by crossing these mice with the Nestin-cre and Isl1-cre mice, and the loss of Hoxc8 expression with or without Hoxc9 mis-expression was confirmed in embryonic spinal cord. In addition, an upregulation of reporter gene expression was observed after Cre-mediated recombination. These mice will be useful tools to analyze Hox gene function in a cell type-specific manner.