The ultrastructural cytochemical reactivity, renin activity, and cathepsin D activity of atria and ventricle of the bullfrog have been assessed. The specific granules (A, B, and D) were found to be argentaphobic when ultrathin sections of Araldite-embedded atria and ventricle were stained according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiery. The entire core of the specific granules was moderated positive after ultrathin sections of glutaraldehyde-fixed, glycol methacrylate embedded atria and ventricle were stained by phosphotungstic acid at a low pH. A similar reaction was shown by the cell coat, intercalated discs, residual bodies (C granules), and Z discs as well as by a very small portion of the Golgi complex. Incubation of ultrathin sections of atria and ventricule fixed only in glutaraldehyde and embedded in glycol methacrylate with either pronase or trypsin resulted in selective digestion of specific granules and Z discs and, to a much lesser degree, of the cell coat. As cathepsin D activity and renin activity were present in both atria and ventricle, the generation of angiotensin I by these cardiocytes might have been due to either enzyme. Nevertheless, because of the glycoprotein nature of specific granules and of the endocrinelike ultrastructure of atrial and ventricular cardiocytes in the frog, the present results raise the possibility that specific granules may contain renin.