A molecular analysis of cross-reactions in costus-sensitive patients reveals that the most active sesquiterpene lactones are the ones with the lesser number of oxygenated substituents close to the alpha-methylene-gamma-butyrolactone ring. Cross-reactions with sesquiterpene lactones with different skeletons (germacranolide and guaianolide or pseudoguaianolide lactones) can probably be explained by concomitant multiple sensitization to two lactones present in costus, respectively costunolide and dehydrocostus lactone.