Interactions of a number of globular proteins with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide were studied. Under conditions of carbodiimide excess at a protein concentration lower than 88.5 x 10(-5) mol/l, the crosslinking reaction was found to proceed exclusively by an intramolecular mechanism. This resulted in conformational changes in the protein secondary structure and decreased its biological activity. At higher protein concentrations, the reaction of intramolecular crosslinking was always the first to proceed, and only then intramolecularly crosslinked proteins interacted. The reaction of intermolecular crosslinking was not followed by a further change in the protein conformation and activity.