The cross-reactivity of IgE antibodies recognizing epitopes of latex allergens and papain was studied in sera of 36 latex-exposed subjects and 22 papain workers. Eight out of 24 latex-sensitized persons also showed a positive reaction to papain in the CAP assay (mostly of low or moderate degree). On the other hand, six out of the 12 sensitized papain workers also revealed IgE binding to latex allergen(s). Reciprocal inhibition experiments confirmed that groups monosensitized to one of the two allergens can be separated from a group showing partial or nearly complete immunologic cross-reactivity. Papain inhibited IgE binding by 20-33% in these subjects, whereas IgE binding to papain was strongly blocked in most cases. Comparison between the primary sequences of Hev b 1, a major latex allergen, and papain suggests that the cross-reactivity may be due to several identical trimers and tetramers.