Cross-sensitivity in allergic contact dermatitis is a simultaneous allergy to 2 or more contact substances which have in common an antigenic determinant or a metabolic derivative. One of the most notable examples is the cross-sensitivity among aromatic compounds which may be oxidized in vivo to benzoquinone (BQ). However, it has also been hypothesized that the allergenicity and cross-sensitization are modulated by the chemical reactivity of the substituents in the para position. A serial dilution of BQ (from 1% to 0.1% in pet.) and three 1,4-substituted benzene derivatives (p-aminophenol, hydroquinone, metol), theoretically capable of conversion to BQ by oxidation, were patch tested in 22 p-phenylenediamine (PPD) positive patients and in 20 controls. The patients and a further 116 subjects with a positive history of sensitivity to 1 or more aminoaromatic compounds were also tested with some haptens of the para group (PPD, p-aminobenzoic acid, p-aminodiphenylamine, benzocaine, procaine chloride, p-toluenediamine sulfate). The results show that (i) the optimal patch test concentration for BQ was 0.2%, (ii) only 4 of the 22 patients allergic to PPD gave a clearly positive allergic reaction to BQ, and (iii) the number of positive reactions to the aromatic compounds was correlated with the presence of activating (-NH2, -OH, -CH3) and deactivating (-COOH) groups in the para position or, perhaps, with their effect on percutaneous penetration. The data suggest that BQ is not the only intermediate in the cross-sensitization of para group haptens. This is probably conditioned by other oxidation products and/or the chemical structure of the substituents in position 4 of the benzene ring.