We are continuing experiments to analyze rapidly frozen cultured rat islets of Langerhans at the level of individual secretory granules. Elemental analysis of thin, dried cryosections has shown that beta (or B) granules can be distinguished by high zinc, calcium, and sulfur, whereas non-beta (mainly alpha, or A) granules contain elevated phosphorus and magnesium. Although a single granule type predominated in a particular cell, some rebel granules were found in A cells that had the compositional fingerprint of B-cell granules. Zinc, which was found in millimolar concentrations in B-cell granules, was considered a marker for the insulin-storage complex. The data indicate that non-B islet cells in the adult pancreas may produce insulin-containing organelles and that, when glucagon and insulin are coexpressed, these hormones are packaged in separate granules. Efforts are now in progress to achieve better freezing conditions and improved quality of cryosections.