BACKGROUND p-Phenylenediamine (PPD)-related chemicals have been used as antioxidants in rubber products, and many cases of contact dermatitis caused by these chemicals have been reported. OBJECTIVE The aim of this study was to investigate relative sensitizing potency and cross-reactivity among PPD derivatives. METHODS Five PPD derivatives, p-aminodiphenylamine (PADPA), N,N'-diphenyl-p-phenylenediamine (DPPD), N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD), N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (DMBPPD), N-(1-methylheptyl)-N'-phenyl-p-phenylenediamine (MHPPD), and the core chemical PPD were evaluated for their sensitizing potency and cross-reactivity using the non-radioactive murine local lymph node assay (LLNA) and the guinea-pig maximization test (GPMT). RESULTS PPD and all the derivatives were identified as primary sensitizers in both tests. The order of potency in the LLNA was as follows: IPPD and PADPA > PPD > DMBPPD and MHPPD > DPPD. In the GPMT, all six groups of animals sensitized with one of these chemicals cross-reacted to four other derivatives. Specifically, the five groups that have a common basic PADPA structure, that is PADPA, DPPD, IPPD, DMBPPD, and MHPPD, all reacted to each other at almost the same scores, while none of them reacted to PPD. CONCLUSIONS The cross-reactivity profile found in the study was to some extent different from that in previous human data, where distinction between cross-reaction and concomitant primary sensitization is not always clear.