1. The nervous system of cephalopod molluscs provides many unusual features which puzzle the biologist. Among these features is a system of nerves passing to the vena cava. Alexandrowicz proposed that this is a neurosecretory system. 2. Examination of the fine structure of the system in Eledone cirrosa shows that the nerves contain many types of vesicle, the most numerous being electron-dense vesicles of 80 - 150 nm diameter. The vesicles are concentrated in the nerve terminals which lie adjacent to the basement membrane found on the inner side of the blood vessel wall. The appearance of the nerves is similar to that of neurosecretory neurons found in both invertebrate and vertebrate nervous systems. Examination of the fine structure of the system in Sepia officinalis demonstrates that a similar arrangement is also present in this cephalopod. 3. Extracts of the vena cava of E. cirrosa exhibit potent pharmacological activity. This activity may be due to one or more active substances. When assayed on the isolated systemic heart of E. cirrosa the active substance causes an increase in amplitude and a prolonged increase in frequency of heartbeat. The regions of the blood vessel demonstrating this activity exactly parallel the distribution of the nerve terminals within the vena cava wall. 4. Structures within the nerve terminals may be isolated on a discontinuous sucrose gradient. It is found that the cardio-excitatory activity is associated with the electron-dense vesicles of 80 - 150 nm diameter. 5. Gel-filtration of vena cava extracts on Sephadex columns indicates that at least two active substances are present, one with a molecular weight less than 5,000 and one with a molecular weight greater than 5,000. 6. Various techniques, i.e. fluorescence histochemistry, spectro- photofluorimetry, and bioassay, reveal that the activity present in the extracts cannot be attributed to the presence of 5-hydroxy- tryptamine or catechol amines. 7. The active substance resists heating at an acid or alkaline pH, is unaffected by evaporation to dryness, and is extractable in organic solvents e.g. acetone. Further analysis is required before the chemical nature of the substance can be determined. 8. Release of the active substance could not be demonstrated to occur after electrical stimulation of the nerve trunks, or by changing the ionic environment of the nerve trunks. 9. The above results support Alexandrowicz' proposal that the nerves passing to the vena cava in Eledone citrosa form a neurosecretory system. The possible functions of this system are discussed.