The influence of polyclonal and monoclonal antibodies, trypsin digestion and mercaptoethanol treatment of C-reactive protein (CRP) in the CRP binding to solid-phase phosphorylethanolamine (PE) has been investigated. Nine monoclonal antibodies reacting with CRP could be divided into at least 2 well-defined groups: one group of 6-7 monoclonals interfering with the binding of CRP to PE (mainly represented by monoclonal 2) and the not interfering with the binding of CRP to PE (mainly represented by monoclonal 5). Trypsin digestion resulted in sequence identified CRP fragments still able to bind to PE and detectable by monoclonal 5 but not by monoclonal 2. On the other hand, binding of CRP to PE was abolished by mercaptoethanol treatment. These results, together with the estimation of the extent of the antigenicity of the PE binding site and the characteristics of the hydrophobicity profile of CRP, suggest that most of the hydrophilic sequences contribute to the PE binding region except a non-overlapping region defined by monoclonal 5. Most probably, some of these sequences are located inside or around the internal bisulphide bridge of each monomer of the pentameric CRP.