3′,5′-Cyclic guanosine monophosphate is the intracellular second messenger regulating phototransduction in mammals. The level of cGMP in photoreceptor cells is controlled by the cGMP-hydrolyzing enzyme cGMP phosphodiesterase and the cGMP-producing enzyme guanylate cyclase. Identification of a photoreceptor-specific guanylate cyclase (retGC) that may function in visual transduction was recently reported. As an initial step in assessing the potential for defects in the retGC (GUC2D) gene to be causal of hereditary retinal disease, we have determined its chromosome location. A 720-bp region of the human GUC2D locus was amplified with exon-specific primers. The amplified product contains three introns, two intact exons, and part of two additional exons, suggesting a high degree of structural complexity. PCR analysis of human-rodent somatic cell hybrids was used to map the GUC2D locus to chromosome 17. This assignment was confirmed and a more precise localization to 17p13.1 was obtained by fluorescence in situ hybridization. © 1994 Academic Press Inc.