Trans-urocanic acid (trans-UCA) is found in the stratum corneum of the epidermis throughout the body and is a major absorber of UV radiation. It converts to cis-UCA on UV exposure in a dose-dependent manner until the photostationary state is reached when approximately equal quantities of the two isomers are present. The action spectrum for the isomerisation shows a maximum at about 310 nm in human skin. HPLC analysis of skin extracts has indicated that the percentage of cis-UCA is elevated in the summer months, even in unexposed body sites, and then returns to background levels in the winter months. There is a 10-fold difference in UCA concentration between human subjects which does not correlate with skin pigmentation, minimum erythema dose, stratum corneum thickness or a past history of skin cancer. UCA does not act as an efficient natural sunscreen. However evidence has accumulated to indicate that cis-UCA is an important initiator of some of the immunosuppressive changes which follow UV radiation. For example, it has down-regulatory effects on epidermal Langerhans cell numbers, delayed hypersensitivity responses, antigen presentation and natural killer cell function. Its mechanism of action is not yet defined, and various possibilities and their implication for photocarcinogenesis and resistance to infectious diseases will be reviewed.