HLA class I is expressed in 75-85 per cent of uveal melanoma and cytoplasmic c-myc expression has been reported in 78 per cent of uveal melanoma. In skin melanoma, an inverse relationship has been observed between HLA class I expression and c-myc. The purpose of this study was to determine whether a similar correlation occurred between high expression of c-myc and low expression of HLA class I in uveal melanoma. The expression of c-myc, HLA-A, and HLA-B was determined by immunohistochemistry on formalin-fixed and paraffin-embedded sections of 30 uveal melanomas. Cell cultures from four primary uveal melanomas (lines 92-1, MEL 202, OCM-1, and EOM-3) and one uveal melanoma metastasis (line OMM-1) were tested for mRNA levels of c-myc and HLA-A and HLA-B in Northern blot assays. The high level of expression of cytoplasmic c-myc was significantly correlated with low expression of HLA-B (P=0β’03) and vice versa. High expression of HLA-B was significantly correlated with the presence of epithelioid cells (P=0β’004). The inverse correlation observed between c-myc and HLA-B expression is similar to previous observations in cutaneous melanoma. By downregulating HLA-B expression, c-myc may influence the immune response in uveal melanoma. Tumours containing epithelioid cells showed a significantly higher expression of HLA-B than tumours of the spindle cell type.