The purpose of this study was to investigate the structure and chemical composition of the mucous skin gland of Xenopus laevis by combined morphological and biochemical techniques. Protein backbones of mucins were localized immunohistochemically in the gland with anti-peptide antibodies. Acid mucins were demonstrated by conventional histochemical techniques and their terminal carbohydrate residues were localized by lectin histochemistry. A close correlation between antibody and lectin binding of the same glycoproteins was achieved on Western blots from isolated skin gland mucins, indicating that the lectin-binding sites were due to defined mucin molecules. The cone cell, thought to be a degenerative cell in the past, contained mucin granules with an electron-dense core, strong PAS reactivity, a special lectin-binding pattern, and localization of integumentary mucins FIM-B.1 and FIM-C.1. These results indicate that cone cells are a distinct cell type, elaborating and releasing particular mucins, and that functional heterogeneity of mucus-producing cells exists in the mucous skin glands of X. laevis.