Serine proteases play essential roles in a wide variety of cellular processes in endocrine cells. There is a growing interest in the roles of serine protease inhibitors, or serpins, as key regulators of their activity. We have cloned two neuroserpin cDNAs from a rat pituitary cDNA library and confirmed tissue plasminogen activator as a potential target for this inhibitor. We show that neuroserpin transcripts are expressed by endocrine cells in the adrenal and pituitary glands and that immunoreactive neuroserpin is stored in densely cored secretory granules in these cells. Overexpression of neuroserpin in an anterior pituitary corticotroph cell line results in the extension of neurite-like processes, suggesting that neuroserpin may play a role in cell communication, cell adhesion, and/or cell migration.