Mutation of the p53 gene which is located on chromosome 17p is the single most frequent alteration observed in human cancer. In this study we evaluate malignant melanoma, the most common intraocular neoplasm in adults, for aberrant p53 expression. Twenty enucleation specimens representing one ciliary body and 17 choroidal melanomas and two choroidal nevi were studied by immunohistochemistry utilizing the D07 anti-p53 antibody and the MIB-1 monoclonal antibody. The tumors included two spindle cell and 16 mixed cell (spindle + epithelioid cell) melanomas and two spindle cell nevi. The MIB-1 labelling index ranged from < 1% (two cases), 1-5% (13 cases) and > 5% (five cases). Of the 18 melanomas, 13 cases showed nuclear p53 staining with the p53 index < 1% (two cases), 1-3% (eight cases) and 4-5% (three cases). No p53 staining was observed in two malignant melanomas of the spindle cell type and in two choroidal nevi. In the 13 malignant melanomas of the mixed cell type, there was no correlation between MIB-1 index and p53 immunoreactivity. Immunopositivity was not found in normal choroidal melanocytes. Our study suggests that p53 alterations may be found in uveal melanomas; in our series, p53 positivity was present only in malignant melanomas of the mixed cell type.