The utility of a preliminary solubility screen has been assessed on ten test proteins. It is proposed that maximizing the protein solubility prior to crystal setups is likely to improve crystal growth. In crystallization setups, drops of a protein solution are mixed with various crystallization solutions which are then allowed to equilibrate. The protein solutions usually contain a salt and buffer which are present as a constant in all crystal screens. The propensity for crystallization, driven by three components of sparse-matrix screens, the buffers, salts and precipitating agents, could potentially be masked by the components of the protein solution. Ten test proteins were dissolved in a standard buffer (100 mM NaCl, 50 mM Tris-HCl pH 7.5) and in customized optimal buffers determined to maximize solubility. The proteins were then subjected to the Index (Hampton Research) 96-well sparse-matrix crystal screen and to a precipitant/precipitant-additive screen described here. Five of the ten proteins studied showed twofold to fourfold increases in the saturation level from standard to optimal buffer, two showed slight improvement and three showed a slight decrease. Microcrystals were obtained for all proteins and optimal buffer increased the appearance of crystals for eight of the ten proteins.