This paper examines lysozyme (LYS) behaviour upon in-vitro digestion, mimicking different conditions in the stomach and intestine, and assessing the effect of natural surfactants, such as phosphatidylcholine (PC) or bile salts (BS), on hydrolysis and residual immunogenicity of the digests. The hydrolysis pattern of LYS was compared to that of alpha-lactalbumin (LA). Hydrolysis of LYS only occurred at low pH. PC slightly increased its resistance to pepsinolysis. A similar behaviour was found for LA. Circular dichroism revealed that the more rigid structure of LYS, as compared with that of LA, could protect it from proteolysis at acidic pH and fluorescence spectra suggested that, at acidic pH, both proteins associated to PC films. The gastric digests of LYS showed high IgE-binding capacity using sera from egg-allergic patients. On the other hand, it was found that LYS precipitated under conditions that simulated a duodenal environment, mainly due to the presence of BS. Published by Elsevier Ltd.