The mouse Bicc1 (mBicc1) gene is the orthologue of the Drosophila Bicaudal-C (Bic-C) gene. While the role of Bicc1 in the mouse is unknown, mutations in the mouse Bicc1 gene are associated with polycystic kidney disease (PKD). The mBicc1 protein contains three K homology (KH) domains. Evidence from other KH domain-containing proteins as well as studies involving both Drosophila and Xenopus Bic-C, suggest that this motif is important in interactions with RNA. RNA-binding assays were used to test whether mouse Bicc1 binds homoribopolymers in vitro. A series of constructs coding for different regions of the mBicc1 protein were used to determine which regions of the mBicc1 protein were important for in vitro RNA binding. Mouse Bicc1 binds homoribopolymers in vitro and the third KH domain is necessary and sufficient for in vitro RNA binding. The mutation responsible for PKD in the jcpk mouse model results in a protein that is incapable of binding RNA in vitro. This study demonstrates that mouse Bicc1, a protein associated with PKD, has the ability to bind RNA in vitro. Disruption of this binding capability may be responsible for cyst formation in animals carrying mutations in the mBicc1 gene.