The effect of solvent conditions on the conformation of rabbit C1q̂ was studied by both spectroscopic and nonspectroscopic methods. The conformation of C1q in buffered saline solutions at pH 7.4 or 6.0 did not differ significantly from C1q at twice the saline concentration as determined with circular dichrosim, difference spectroscopy and tritium-hydrogen exchange techniques. Addition of calcium to the buffers had no structural effects in any of the conditions examined. Hydrogen exchange experiments performed at pH 7.4 were also unaffected by Mg++, Mn++ or ethylenediaminetetraacetic acid. With all the methods used a pH effect was observable between 5.1 and 8.3. From solvent perturbation difference spectroscopy results it was calculated that the equivalent of 9.7 and 6.2 moles of Tyr and Try, respectively per mole of C1q, become exposed at the lower pH. These changes suggest alterations in globular parts of the molecule.