A reversed phase HPLC technique has been applied to measure the loss of solubility (at pH 4.6) of alpha-lactalbumin and beta-lactoglobulin resulting from the spray drying of whey protein isolate solution. Spray drying was performed in a pilot-scale co-current spray dryer with different feed concentrations (20-40% w/v) and outlet temperatures (60-120 degrees C). The study reveals that the solubility of both alpha-lactalbumin and beta-lactoglobulin was not significantly affected at low outlet gas temperatures (60-80 degrees C), but was strongly affected (up to 40%) at high temperatures (100-120 degrees C). Significantly higher losses in solubility were observed for beta-lactoglobulin compared to alpha-lactalbumin. Increasing the feed concentration at higher outlet temperatures also caused noticeable increases in insolubility. The reversed phase HPLC results were consistent with those from total protein nitrogen content (Kjeldhal) analyses. (C) 2007 Swiss Society of Food Science and Technology. Published by Elsevier Ltd. All rights reserved.