Retina cognin (R-cognin) is a 50 kDa protein involved in cell recognition and neuronal differentiation during development of the embryonic chick retina. Initial characterization of a partial cDNA encoding R-cognin revealed a striking similarity to the cDNA encoding protein disulfide isomerase (PDI), a 57 kDa multifunctional protein. The exact nature of the relationship between R-cognin and PDI is not known; however, both proteins appear to be encoded by the same gene. In the present study, we developed cRNA probes to examine the expression of R-cognin and PDI transcripts in embryonic chick retina and liver. In the retina, the amount of transcript decreased with embryonic age, in parallel to a similar decrease in R-cognin protein. In the liver, where PDI is prominently expressed, the amount of transcript was not developmentally regulated. The spatial and temporal pattern of expression of the R-cognin-encoding retinal transcript was examined by in situ hybridization. R-cognin mRNA was expressed in cells across the retina early in retinogenesis, but became restricted to the cells of the inner retina later in development. This pattern of expression was the same as the developmental pattern of R-cognin protein [Dobi et al., Invest. Ophthalmol. Vis. Sci. 27, (1986) p. 323-329], thus, demonstrating that this secreted protein functions at the surface of the cells where it is transcribed.