1. The proteins of large dense-core vesicles (LDV) in neuroendocrine tissues are well characterized. Secretory components comprise chromogranins and neuropeptides. Intrinsic membrane proteins include cytochrome b-561, transporters, SV2, synaptotagmin, and synaptobrevin. 2. The effects of stimulation and of second messengers on the biosynthesis of LDV have been studied in detail. 3. Regulation of biosynthesis is complex. The cell can adapt to prolonged stimulation either by producing vesicles of normal size filled with a higher quantum of secretory peptides or by forming larger vesicles. In addition, some components, e.g., enzymes, can be upregulated specifically.