The plasma level of mucosal mast-cell protease was examined to find whether such measurements could be an indicator of allergic response to beta-lactoglobulin (beta-LG) challenged orally by rats. Brown Norway rats, which had been raised on a bovine milk-free diet, were systemically sensitized on day 0 with a low dose of beta-LG, and then by an oral administration of beta-LG for 3 h on day 14. The oral challenge with beta-LG in saline, when compared to saline alone, resulted in a systemic elevation of rat mast-cell protease II (RMCPII), one of the specific markers for gut mucosal mast-cell secretion. The challenge with beta-LG in a fat emulsion further increased the level of plasma RMCPII. This manipulation, however, was not successful for detecting any significant difference in mucosal leucotriene C4, another allergic mediator. An oral challenge with polymerized beta-LG did not induce any elevation of the protease, but resulted in a lower plasma level of beta-LG-specific IgG. This animal model is thus relevant to investigate the events regulating the mucosal hypersensitivity and humoral immunity to food proteins.