The high mortality rate of melanoma patients who develop metastases prompted us to look for prognostic markers to determine high-risk and non-risk patients at the primary tumour stage. Therefore, we quantified plasma concentrations of soluble HLA class I antigens (sHLA-I) by ELISA in patients with primary tumours (MM-P) and with metastases (MM-M), respectively, and compared them to a control group. Whereas healthy probands (n = 55) and MM-M (n = 38) showed similar mean values of sHLA-I (1.30 +/- 1.44 micrograms/ml and 1.29 +/- 1.27 micrograms/ml), MM-P (n = 67) revealed significantly reduced levels of this marker (0.84 +/- 0.85 microgram/ml). This result matches with our immunohistological staining of membrane-bound HLA-I in sections of paraffin-embedded melanoma. Further subdivision of the MM-P substantiated the observation that mean values of decreased sHLA-I concentrations are in line with high tumour thickness. Since the beginning of this study (1990) to date, 11 of 67 MM-P have developed metastases. The prognostic efficiency of sHLA-I to identify high-risk and non-risk patients was tested by ROC-analysis (receiver operating characteristic) and did not demonstrate good prognostic relevance for sHLA-I (W = 0.64, p = 0.04).