The conformation of porcine-brain calmodulin in solution has been examined by far-UV circular dichroism in the presence of 2-methyl 2,4-pentanediol, and polyethylene glycol which are used to promote the crystallisation of calmodulin. These organic compounds increase the alpha-helical content of Ca4-calmodulin to a significant degree and to a level similar to the alpha-helical content deduced from the crystal structure. These results support the view that in aqueous solution at pH 5-7, the conformation of Ca4-calmodulin is significantly different from the crystal structure and probably lacks at least a portion of the central helix. In the process of crystallisation, Ca4-calmodulin apparently adopts additional alpha-helical structure, probably due to the composition of the solution from which crystals are grown.