Abstract. Seven hundred patients were investigated prospectively before undergoing chemonucleolysis. A past history of allergy and/or previous exposure to papain, either in food, beverages or drugs, was sought, and a skin-prick test with chymopapain was performed. Based on the results obtained, the subjects were classified into four groups: Group I– 225 non-atopic non-papain-exposed subjects; Group II–285 non-atopic papain-exposed subjects; Group III–69 atopic non-papain-exposed subjects; and Group IV– 121 atopic papain-exposed subjects. Latent sensitization to papain was observed in 0.4% of subjects in Group I, 3.16% in Group II, 5.8% in Group III and 7.4% in Group IV. The odds ratios were 13.8 for atopy and 7.3 for exposure to papain. Interaction between atopy and papain exposure did not result in a significantly greater risk. Neither sex nor age nor a history of a previous drug reaction were risk factors. Only one patient out of the 23 who were sensitive to papain had no risk factor. The 677 skin-test negative patients then underwent chemonucleolysis and none of them had an anaphylactic reaction. This was significantly less frequent: (P= 0-04) than the incidence in a random population (0.45%). Prick tests performed 6 weeks and 6 months after chemonucleolysis revealed newly acquired sensitization in 36% of the patients. Atopy was not a risk factor for this event. Three points are discussed: (i) the negative predictive value of skin-prick tests with chymopapain is confirmed; (ii) subjects likely to be sensitized are atopic and/or have been exposed previously to food or drugs containing papain and therefore they can be identified pre-operatively by a questionnaire; (iii) atopy is a risk factor for the induction of specific IgE to allergens internalized via a mucosal surface but not for those that are injected parenterally.