Crossreactivity of IgE antibody against Dermatophagoides farinae (Der f) with Limulus polyphemus agglutinin (LPA) was examined using RAST and immunoblot analysis. Of 40 Der f-sensitive asthmatic patients, 28 revealed a positive RAST reaction to LPA, while none of 20 Der f-insensitive hay fever patients showed this reaction. LPA-specific RAST levels of the 40 asthmatic patients correlated with their Der f-specific levels. The RAST reactivity to LPA was competitively inhibited by the addition of either soluble Der f or LPA, but not by the specific inhibitory sugar of sialic acid. LPA could also induce histamine release from leucocytes of Der f-sensitive asthmatic patients. IgE immunoblot analyses showed that the positive RAST sera for LPA had a strong IgE binding activity to the 30 kDa and 80 kDa components of Der f body extract, whereas gel filtration studies showed that the high molecular weight fractions above 150 kDa retained antigenic constituents associated with IgE reactivity to LPA. These results suggest that the antigenic materials of Dermatophagoides mites share some determinants with the haemagglutinin of horseshoe crabs.