A novel cuvette was used to subject citrated platelet-rich plasma (PRP) to high hydrostatic pressure with negligible contamination by He (used for compression of the apparatus). Aggregation was induced at pressure by ADP and quantified turbidimetrically. The maximum degree of aggregation (MDA) was reduced from a control level of 82.2 to 53.6% by exposure to 101 ATA. Because decompression bubbles did not form, aggregation was also measured immediately after a compression cycle. After exposure to 101 ATA hydrostatic pressure, platelets responded normally to ADP at 1 ATA. In a matching apparatus, PRP was equilibrated with high partial pressures of inert gases. Normal physiological plasma Po2 and pH were maintained during equilibration. N2O (5 ATA) reduced the MDA from 86.5 (control) to 58.1%. N2 (51 ATA) reduced the MDA from 74.7 (control) to 51.6%, and 101 ATA Pn2 reduced the MDA from 78.0 (control) to 32.3%. He (100 ATA) reduced the MDA from 83.6 to 38.6%. It was concluded that platelet aggregation was relatively sensitive to hydrostatic pressure and less sensitive to inert gases than predicted from their anesthetic potency ratios.