At low ionic strength (0.05 M) the sedimentation coefficient of monomeric plasma fibronectin was found to vary from 8S, at pH 3 and 11, to 13.5S at neutral pH. The lower s20,w value indicates a stretched arrangement of the value indicates a stretched arrangement of the two arms of the molecule which was observed in most electron microscopic studies. The higher value is consistent with a still very asymmetric but more condensed shape, which is probably brought about by back-folding and interactions between chain segments of different net charge. A model of this internal association is based on the finding that segments of rather different isoelectric points alternate along the fibronectin chains. A similar pH dependence was observed for a 140-kDa fragment from the middle region of fibronectin which carries segments of low and high isoelectric points at its ends. At high ionic strength (0.35 M) the pH dependence of the sedimentation coefficients was less pronounced and intermediate s20,w values were found. This is expected when both repulsive and attractive interactions are weakened by the electrolyte. It was verified by circular dichroism spectra that the protein was not denatured at pH 3 or 11. Thermal transition curves revealed a destabilization at pH 3 but the thermal denaturation occurred well above 20 degrees C at which the pH dependence of the solution shape was studied.