The structure of six human myeloma proteins: IgGl(Bal), IgG2(Klu), IgG3(Bak), IgG3(Het), IgG4(Kov) and IgG4(Pol), was studied in solution using small-angle X-ray scattering and hydrodynamic methods. For IgGl (Bal) and IgG3(Het) the experimental data, including radius of gyration (R",), radii of gyration of the cross-section (Rql, RqJ, intrinsic viscosity [q], sedimentation coefficient SO^^,^) and molecular mass, were interpreted in terms of structural models based on the Fab and Fc conformations, observed in crystal, by varying the relative positions of the Fab and Fc parts, i.e. their relative angles and distances. IgGl(Ba1) can be resolved by proposing a 'non-planar' (tetrahedral) molecular shape, in which the long hinge peptide is in a folded conformation and the two Fab and Fc parts are in a closely packed arrangement. In this model the angle between the two Fab arms is about 90", in the average position.The X-ray scattering and hydrodynamic behaviour of the IgG2 and IgG4 types of antibodies appeared to be similar to IgGl(Ba1). The parameters of the two IgG3 proteins are similar while they are different to the others.Immunoglobulins are closely related proteins having a common fundamental structure. Based on differences in the constant part of the molecules, human immunoglobulins are classified into five classes. The most abundant human immunoglobulin class, IgG, is a mixture of four subclasses with differing structure and antigenic types of the heavy chains [I -31. The functional significance of the existence of the four IgG subclasses is not completely clear, although subclassrelated differences in complement fixation [4] [8, 18, 271. The proposed structures indicate the dominating differences in the y chains which are localized in the hinge region [29]. It is known that the structure of the hinge region can influence the segmental flexibility within the IgG molecules and it plays a role in their overall structure [I 1, 12,301. However, our knowledge about the conformation and the functional role of the hinge region is far from complete. Substantial differences have been described in the primary structure of the hinge [29] among human IgG subclasses; therefore, these proteins offer a good system for comparative studies to answer the question of whether the differences in the hinge sequence are reflected in the overall conformation of IgG. Since IgG molecules function as intact, dissolved particles, our aim was to conduct solution studies on complete IgGs. Myeloma proteins are homogeneous monoclonal populations representing a single subclass and, therefore, provide suitable systems for such physico-chemical studies. Smallangle X-ray scattering and hydrodynamic methods were chosen as the best applicable methods to provide information about the overall shape of macromolecules in solution.Particular care was taken to avoid aggregate formation in the X-ray scattering measurements. Our attention was focussed on the structural differences between the most abundant'IgG1 and the controversial IgG3 subclasses....