Pressures on the order of 1000-4000 bar have been reported to reversibly dissociate a number of oligomeric protein complexes without gross changes in protein structure. Here, we report that hydrostatic pressure can also dissociate some antigen-antibody complexes in solution. The association of fluorescent-labeled antigens with monoclonal antibodies was monitored via increases in the fluorescence anisotropy upon binding. Previously, we had found that pressures of 2000 atm were able to dissociate bovine serum albumin (BSA) from immunoadsorbents formed from certain antibodies but not others. In this study, we have found that the sensitivity to pressure in solution is present for the interaction of BSA with MAb 9.1 and absent for the interaction of BSA with MAb 6.1; this behavior is consistent with the immunoadsorbent study. The interaction of hen egg white lysozyme with two monoclonal antibodies was also measured. Interestingly, the complex with the greater electrostatic character (HyHEL-5) did not exhibit pressure sensitivity, as would be expected due to electrostriction effects, whereas the more hydrophobic complex (HyHEL-10) exhibited a strong pressure sensitivity. In each of the systems displaying pressure sensitivity, the free energy of association was found to increase linearly with pressure, indicating a constant change in volume between the free and bound states. Overall, these results indicate that some antigen-antibody complexes exhibit significant sensitivity to pressure, whereas others do not; the mechanisms that discriminate between these cases remain unresolved. Understanding and manipulation of this phenomenon may prove useful in a variety of processes involving the recovery from antigens of antibodies.