On exposure to UV-B, the epidermal component trans-urocanic acid (UCA) is not only photoisomerized into cis-UCA but will also, at least in part, be photooxidized into UCA oxidation products (UOPs). We hypothesized that UOPs can mimic UV-induced systemic immunosuppression comparable to the suppressive properties already established for cis-UCA. A crude mixture of UOPs showed a significant suppression of the sensitization phase of the systemic contact hypersensitivity (CHS) response to picryl chloride (PCl). Three of the UOPs were selected for this study: imidazole-4-carboxylic acid (ImCOOH), imidazole-4-carboxaldehyde (ImCHO) and imidazole-4-acetic acid (ImAc). Effects on the sensitization, elicitation and postelicitation phases of CHS to PCl in BALB/c mice were studied and compared with the effects of cis-UCA. ImCHO was equally effective at suppressing the sensitization phase as cis-UCA. The triplet combination of the imidazoles (1:1:1) showed more pronounced suppression than that induced by cis-UCA. The most effective compounds for the suppression of the elicitation phase appeared to be ImAc and cis-UCA. Significant suppression of the postelicitation phase was only obtained with the triplet combination of ImCHO, ImCOOH and ImAc, the combination that appeared to be effective at all three tested phases. Because these three UOPs are present in UV-B-exposed human stratum corneum, these compounds may play a role in UV-B-induced immunosuppression.