In this study response surface methodology (RSM) was used to optimize the spray drying process conditions for production of kefir powder. Influence of inlet air temperature (120-180 degrees C), feed temperature (4-30 degrees C) and pump rate (20-40%) on the survival rates of microorganisms, outlet temperature, moisture content and water activity were assessed after drying and modeled by RSM. A lab-scale spray dryer (Mini Spray Dryer B-290, Switzerland) was used to carry out the drying experiments which are planned according to Central Composite Rotatable Design (CCRD). Inlet temperature was found as the main factor that effects the all responses statistically significant (p < 0.05). Effect of pump rate on the responses was found significant for some responses. Feed temperature has no significant effect for any responses. The optimum conditions were found as 135 degrees C inlet air temperature and 35% pump rate with using Desirability Function. Desired parameters were determined in regard to model fit and lack of fit test analysis results. At the end of this study, optimum conditions of spray drying were matched with freeze drying results. Results showed that at the optimum point, good quality powder can be obtained as freeze dried powder quality. (C) 2014 Elsevier Ltd. All rights reserved.