Colony stimulating factor‐1 (CSF‐1) is the primary regulator of the mononuclear phagocytic lineage acting through its transmembrane tyrosine kinase receptor, CSF‐1R, that is the product of the c‐fms proto‐oncogene. Null mutations in either the ligand or the receptor genes result in a severe osteopetrosis as well as a number of other phenotypes, including reproductive defects and perturbations in organ development. The CSF‐1R is also expressed in oocytes, myoblast progenitors, decidual, and trophoblastic cells. To distinguish cell type specific phenotypes, we have created a conditional allele of the Csf1r by placing LoxP sites around Exon 5 of the Csf1r gene in mice. Excision of this floxed sequence results in a null allele that in the homozygous state gives a phenotype indistinguishable of the complete Csf1r null mutant mouse. This conditional allele will prove extremely valuable to study the spatial and temporal roles of CSF‐1R. genesis 44:328–335, 2006. © 2006 Wiley‐Liss, Inc.