Up to now, systematic studies on protein interactions in solution have been (mostly) restricted to small molecular weight model proteins like lysozyme, BPTI or gamma-crystallins. Those studies involving a combination of techniques (osmotic pressure, light scattering, small-angle X-ray scattering, etc.) led to an interpretation of the results in terms of interaction potentials, the parameters of which can be related in a semi-quantitative way to van der Waals forces and particle charges. We have undertaken an X-ray scattering study to extend the interaction potential analysis to the case of a large size oligomeric protein, aspartate transcarbamylase from E. coli. This heterododecamer comprises two trimers of catalytic chains and three dimers of regulatory chains for a total molecular weight of 306 kDA. It is a slightly acidic protein (pI = 5.9). The main thermodynamic and chemical parameters were varied: temperature, protein concentration, pH, salt nature and concentration. Moreover, we took advantage of the large molecular weight of ATCase to study the effect of polyethylene glycols. The results are compared to those reached in the case of small proteins. (C) 1999 Elsevier Science B.V. All rights reserved.