The high pressure neurological syndrome (h.p.n.s.) constitutes a major barrier to deep sea exploration by man. Although the signs and symptoms of h.p.n.s. are well documented in both man and experimental animals, the underlying mechanisms remain to be elucidated. Physiological and pharmacological evidence will be presented that confirms that the principal sites of action of pressure are within the central nervous system (c.n.s.). Results from physiological studies not only indicate that there are separate sites of action of pressure within the c.n.s., which mediate the different components of h.p.n.s., but also the response to pressure may be controlled by descending inhibitory pathways. Pharmacological studies support this view and suggest that h.p.n.s. involves a failure of central inhibition.