A successful development of therapeutic proteins requires a formulation optimal for long-term storage of the proteins. During storage and shipment, proteins are subjected to multiple stresses. Here we show that ciliary neurotrophic factor (CNTF) readily aggregates upon exposure to mechanical stress such as agitation and elevated temperature at 37°C. Sucrose and lysine or arginine protect CNTF from heat stress, while detergents such as Tween20 and organic solvents such as propylene glycol (PG) are effective against agitation. Combination of the amino acids and PG protected the protein from both stresses. The results suggest the importance of combining additives, against multiple stresses, which may have negative as well as positive influence individually against one particular stress.