A comparison of the solution structure of the interleukin-8 dimer determined by nuclear magnetic resonance spectroscopy with that of the 2 A resolution X-ray structure, solved by molecular replacement using the solution structure as a starting model, is presented. At the monomer level the atomic root-mean-square difference between the two structures for residues 7 to 72 is approximately 1.1 A for the backbone atoms, approximately 1.6 A for all atoms, and approximately 1 A for all atoms of the internal residues. There are two main regions of difference in the monomer. In the X-ray structure residues 4 to 6 are well ordered and the charged groups of Glu4 of one subunit and Lys23' of the other are in close enough proximity to form an electrostatic interaction. In contrast, these residues are partially disordered in solution and the electrostatic interaction involving Glu4 is replaced by one between Glu29 of one subunit and Lys23' of the other. In the loop comprising residues 31 to 36, His33 accepts a hydrogen bond from the backbone amide group of Gln8 in the solution structure, but donates a hydrogen bond to the backbone carbonyl group of Glu29 in the X-ray structure. There is also a difference in the quaternary structure with regard to the relative orientation of the two subunits produced by a rigid body rotation about the C2 axis that alters the angle between the central beta-strands (formed by residues 23 to 29 of the 2 subunits) at the dimer interface, without breaking the symmetry. In the solution structure this angle has a value of 168 degrees, while in the X-ray structure the central strands are essentially flat, with an angle of 179 degrees. As a result, the separation between the two anti-parallel helices, which lie at an angle of about 60 degrees to the underlying beta-strands, is decreased from 14.8 A in the solution structure to 11.1 A in the X-ray structure. The quaternary structural difference is related to the different conformations of the N terminus and the 31 to 36 loop, both of which display different interactions with respect to the ends of the central beta-strands in the two structures. These findings indicate that interleukin-8 has the potential to undergo conformational transitions that may be of functional significance.