Groups of rats previously sensitized systemically on day 0 with a low dose of ovalbumin (OVA) were gavaged daily with ovalbumin or bovine serum albumin or a mixture of both proteins from day 14 to 18. Blood samples were obtained pre- and post-challenge and serum levels of the rat mast cell protease II (RMCPII) determined by immunoassay. Release of this specific mucosal mast cell mediator was only observed in animals challenged with ovalbumin and the initial challenge released levels of RMCPII 15-fold higher than normal resting levels (P < 0·001). Subsequent daily challenges evoked the release of significantly lower levels of mediator (P < 0·00l relative to day 14), but with one exception each test group released significantly more RMCPII than the matched control group on each day (P < 0·001 =P= 0·015). An increased uptake of BSA ‘bystander’ protein was observed when OVA-sensitized animals were repeatedly gavage-challenged with OVA but there was no correlation with the release of RMCPII mediator. After a 9-day rest period the levels of RMCPII released 6 hr post-challenge on day 26 were still significantly lower (P= 0·004) than the levels of mediator released on day 14. In contrast, animals not previously challenged were still capable of releasing high levels of mediator at the time of first mucosal contact. The levels of RMCPII detected in the serum after enteral protein antigen challenge never exceeded 6000 ng/ml and were lower than those previously observed in parasitized rats following intravenous antigen challenge.