One hundred and six squamous cell carcinomas (SCCs) of cattle, horses, cats and dogs were analysed immunohistochemically for overexpression of p53 protein. The monoclonal antibody pAb 240, which recognizes only mutant p53, was used. Of 41 bovine ocular SCCs, 26 (63.4%) showed p53 nuclear reactivity. All of six (100%) equine ocular SCCs and seven of nine (77.7%) SCCs of the equine penis or vulva gave positive reactions. In nine of 11 (81.8%) feline SCCs of the ear and in seven of 14 (50%) feline SCCs of other locations, p53 immunoreactivity was detected. Only seven of 25 (29.5%) canine cutaneous SCCs gave a positive reaction. Thus p53 antigen could be detected immunohistochemically in formalin-fixed and paraffin wax-embedded tissues of SCCs of domestic animals. The results support the view that, as in man, p53 overexpression plays an important role in the development of most SCCs of the animal species studied. This was in particular true for feline SCCs of the ear and for bovine and equine ocular SCCs, which are assumed to be related to ultraviolet radiation.