Choroid plexus (CP) development may depend on an inductive interaction between primordial CP epithelium and the overlying mesenchyme. Expression of the two CP epithelial-expressed genes, transthyretin (TTR) and insulin-like growth factor II (IGF-II), were studied by in situ hybridization in the developing rat. Transthyretin mRNA is expressed in abundance in the primordial CP epithelium prior to CP morphogenesis (e10-11) but IGF-II mRNA expression begins later (e13) and increases gradually as morphogenesis proceeds. In the CP stroma (mesenchyme), IGF-II mRNA is abundant prior to CP morphogenesis but decreases as embryogenesis proceeds and is absent in the adult. Our findings suggest that IGF-II may play an early paracrine and later autocrine role in CP development. A model is proposed in which IGF-II synthesized by mesenchyme serves as an inducing principle for CP epithelial differentiation.