Information on very high pressure (VHP) effects on proteins is limited and therefore effects of VHP on chemistry, structure and function of two model proteins in medical use were studied. VHP (8 GPa) application to l-asparaginase (L-ASNase) resulted in faster mobility on clear native gels. VHP induced generation of lower-MW forms of L-ASNase but VHP treatment did not deteriorate asparaginase activity. Electrophoretic patterns in native and denaturing gels were comparable for untreated and pressurized recombinant human growth hormone (rhGH). rhGH function, however, was deteriorated as shown by a bioassay. In L-ASNase and rhGH a series of protein modifications and amino acid exchanges (indicating cleavage of covalent bonds) were revealed that may probably lead to functional and conformational changes. The findings have implications in protein chemistry, structure, and function and are useful for designing biotechnological applications of protein products.