The distribution of the messenger ribonucleic acids (mRNAs) for chromogranin A and B was analyzed by in situ hybridization in normal and neoplastic endocrine tissues using frozen and paraffin tissue sections. Combined in situ hybridization and immunochemical staining was also done on tissue sections from the same cases using a monoclonal antibody against chromogranin A (LK2H10). Most endocrine tumors expressed chromogranin A and B mRNAs as well as chromogranin A protein. Normal pituitary expressed chromogranin A and B mRNAs and chromogranin A protein in the anterior pituitary gland. Most of these cells were gonadotropic hormone-producing cells. Prolactinomas (5/5) did not express chromogranin A mRNA or protein, but contained chromogranin B mRNA. Null cell or nonfunctional adenomas (8/8) expressed chromogranin A and B mRNAs and reacted with antibody LK2H10. In some tumors such as Merkel cell carcinomas, insulinomas, and parathyroid adenomas, a stronger signal for chromogranin A mRNA was detected than for the immunoreactive proteins. These results indicate that in situ hybridization complements immunochemical techniques in the analysis of endocrine cells and neoplasms. The gene products for chromogranin A and B are widely distributed in many endocrine cells and tumors, but some neoplasms such as prolactinomas have a differential distribution of chromogranin A and B mRNA and proteins.