This chapter discusses immunohistochemical visualization of cyclic nucleotides. Cyclic nucleotides are small, water-soluble, nonimmunogenic molecules. They, therefore, need to be conjugated to a carrier protein, and then antibodies can be raised to these haptens. The chemical properties of cyclic nucleotides are not promising in this respect when tissue preservation and cellular morphology have to be taken into account. Ideally, the chemical reaction that fixes the hapten to the immunogenic carrier protein should be the same as when fixing the antigen to the tissue protein in preparing the tissue for immunocytochemistry (ICC). Specificity testing of antisera is of the utmost importance. In earlier studies, the cAMP and cGMP antisera fulfilled all the criteria necessary for a specific recognition of cAMP and cGMP, respectively. Application of preimmune sera or preabsorption of the antisera with the respective conjugates resulted in no immunostaining. Cyclic GMP is synthesized by the enzyme guanylate cyclase (GNC). Two families of isoenzymes can be distinguished: (1) the particulate, plasma membrane-bound GNC (pGNC), and (2) the cytosolic, soluble GNC (sGNC).