The reaction of cytochrome P450(cam) with aryldiazenes (ArN=NH) yields sigma-bonded iron-aryl (Fe-aryl) complexes. Oxidation of the complexes causes regioselective migration of the aryl group from the iron to the porphyrin nitrogens. The influence of high pressure on the formation and rearrangement of the Fe-aryl complexes is reported here. The natural logarithm of the rate of formation of the Fe-phenyl complex decreases linearly with pressure with a volume of activation of 38.2 mL mol(-1). The Fe-phenyl, Fe-(2-naphthyl), and Fe-(p-biphenyl) complexes are stable at atmospheric pressure but decompose in a pressure-dependent manner at pressures above 1500 (Fe-phenyl) or 2500 bar (Fe-(2-naphthyl) or Fe-(p-biphenyl)). This pressure-induced decomposition results in formation of the N-arylprotoporphyrin IX adducts. The N-aryl porphyrin regioisomer patterns obtained by pressure-induced migration of the aryl groups (N-B:N-A:N-C:N-D, Ph, 10:14:33:43; 2-naphthyl, 12:13:37:38; p-biphenyl, 15:15:33:37) differ from those obtained by oxidation of the P450(cam) Fe-aryl complexes at atmospheric pressure (Ph, 00:05:25:70; 2-naphthyl, 00:00:100:00; p-biphenyl, 00:14:40:46). Preincubation of P450(cam) at elevated pressure followed by decompression, Fe-phenyl complex formation, and oxidative shift yields the same N-phenyl regioisomer ratio as the pressure-induced shift. The three principal findings of this study are that (a) the iron-to-nitrogen migration of the aryl group can be promoted by pressure, (b) differential distortion of the P450(cam) active site by high pressure causes small displacements of the I-helix and residues associated with the substrate access channel, and (c) pressure causes a subtle structural change in the P450(cam) active site that persists at atmospheric pressure.