Tumour necrosis factor-alpha (TNFalpha) is a cytokine with a variety of biological activities, including an effect on tumour growth. The soluble TNF receptor TNF-R55 (sTNF-R55) inhibits TNFalpha functioning. Serum values of TNFalpha and TNF-R55 have been observed in patients with different cancers. To determine the serum values of TNFalpha and its soluble receptors and to investigate the prognostic value of sTNF-R55, we studied the sera of 68 patients with metastatic melanoma, 109 patients with no recurrent disease after surgical removal of melanoma, and 69 healthy controls. At least four different monoclonal antibodies against human TNFalpha and human TNF-R55, respectively, were prepared to obtain sensitive and reliable sandwich enzyme-linked immunosorbent assays. We found that in patients with metastatic melanoma the serum values of sTNF-R55 were significantly higher (2.41 ng/ml; range 0.02 23.0 ng/ml; P < 0.05) than in the melanoma patients without recurrence (0.54 ng/ml; range 0.02-6.25 ng/ml) and healthy controls (0.5 ng/ml; range 0.02 5.0 ng/ml). The sTNF-R55 concentrations increased as the disease progressed. Patients with metastatic melanoma also had significantly higher concentrations of TNFalpha (3.34 ng/ml; range 0.03-30.0 ng/ml; P<0.05) than patients without recurrence (1.24 ng/ml; range 0.02 23.0 ng/ml). Patients with metastatic melanoma, a high sTNF-R55 concentration, a low TNFalpha concentration and a low TNF:sTNF-R55 ratio had the worst prognosis. Low values of sTNF-R55 (<0.6 ng/ml) were associated with favourable response to chemotherapy (P = 0.007). According to our findings, patients with metastatic melanoma have higher values of sTNF-R55 than the controls and melanoma patients without recurrence. sTNF-R55 values higher than 0.6 ng/ml and a TNF:sTNF-R55 ratio lower than 1.5 are unfavourable prognostic factors for response to chemotherapy.