Opalescence and high viscosities can pose challenges for high concentration formulation of antibodies. Both phenomena result from protein-protein intermolecular interactions that can be modulated with solution ionic strength. We studied a therapeutic monoclonal antibody (mAb) that exhibits high viscosity in solutions at low ionic strength ( approximately 20 cP at 90 mg/mL and 23 degrees C) and significant opalescence at isotonic ionic strength (approximately 100 nephelometric turbidity units at 90 mg/mL and 23 degrees C). The intermolecular interactions responsible for these effects were characterized using membrane osmometry, static light scattering, and zeta potential measurements. The net protein-protein interactions were repulsive at low ionic strength ( approximately 4 mM) and attractive at isotonic ionic strengths. The high viscosities are attributed to electroviscous forces at low ionic strength and the significant opalescence at isotonic ionic strength is correlated with attractive antibody interactions. Furthermore, there appears to be a connection to critical phenomena and it is suggested that the extent of opalescence is dependent on the proximity to the critical point. We demonstrate that by balancing the repulsive and attractive forces via intermediate ionic strengths and by increasing the mAb concentration above the apparent critical concentration both opalescence and viscosity can be simultaneously minimized.