In order to investigate the mechanism of urocanic acid (UCA)-mediated immune modulation, we studied the effect of cis- and trans-UCA on interleukin-1 beta and tumour necrosis factor-alpha production by human peripheral blood monocytes, using immunospecific ELISA techniques. Trans-UCA augmented the interleukin-1 beta production and inhibited tumour necrosis factor-alpha production in a dose-dependent manner, whereas cis-UCA had no effect on the secretion of these cytokines by phorbol myristate acetate or lipopolysaccharide-stimulated monocytes. This is a novel example of trans-UCA mediating a biological effect, a finding earlier reported for cyclic adenosine monophosphate up-regulation in human fibroblasts by Palaszynski and coworkers and for human natural killer cell inhibition by ourselves. Our data suggest an important role for trans-UCA as an immunomodulator in the skin.