It has been proposed that the cross-reactions seen clinically between hydroquinone and para-phenylenediamine (PPD) arise from the formation of a common hapten, benzoquinone, in vivo, and that these chemicals therefore represent "prohaptens". A series of 1,4-substituted benzene derivatives has been used to examine this prohapten concept in the guinea pig model. Using both topical and intradermal routes of application, it is demonstrated that in the guinea pig 1,4-substituted benzene derivatives capable of oxidation to benzoquinone, including hydroquinone and PPD, show only restricted evidence of cross-reactions. These results support the prohapten concept. However taken in combination with data on cross-reactivity with 1,2- and 1,3-substituted benzenes, rather than giving rise to a single common hapten, they can be more readily interpreted as the formation of a spectrum of antigenic determinants in vivo, some of which are shared in common.