Purpose. Solutions of the bovine lens proteinγB (orγII) crystallin at neutral pH in the absence of reducing agents, undergo a slow, partial conversion to a new protein species,γIIH. This species is an aggregate composed of an intermolecular, disulfide-crosslinked dimer (≈32% of total protein by weight) and loosely associated dimers (≈66%).γIIHhas a phase separation temperature (Tph), at least 40d`C higher than that of nativeγII crystallin at any given protein concentration. In this paper we demonstrate that pantethine, a derivative of coenzyme A, inhibits the formation ofγIIH.Methods.γII crystallin solutions were incubated at pH 7.1 and room temperature with increasing amounts of pantethine. The Tphof the solutions was monitored as a function of incubation time. Corresponding to each Tphmeasurement, aliquots of each solution were analyzed by cation-exchange HPLC to determine the amount ofγIIHformed.Results. Incubation ofγII crystallin with increasing amounts of pantethine lowers Tphand suppresses the formation ofγIIH. With pantethine to protein mole ratios of 0.66, 1 and 2, the TphofγII crystallin is lowered from 8d`C in the native protein, to 2d`C, -3d`C and -4.3d`C respectively, at a protein concentration of≈200 mg/ml. The amount ofγIIHaccumulated decreases from∼25% in the native protein to 10%, 1% and 0% respectively in these pantethine-trcatcd protein solutions. For complete suppression of the rise in Tphand inhibition ofγIIHformation, a 2:1 mole ratio of pantethine to protein is required.Conclusions. We suggest that pantethine reacts with two cys-leine residues ofγII crystallin by forming a mixed disulfide, and effectively suppresses protein aggregation and lowers Tph. This is due to the strong polar character of pantethine which reduces the net attractive interactions between the protein molecules.