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Serum S100B and lactate dehydrogenase (LDH) levels were evaluated for their ability to predict response in patients with metastatic malignant melanoma and to determine their usefulness in monitoring the results of chemoimmunotherapy. Levels were studied in 53 patients with metastatic malignant melanoma receiving chemoimmunotherapy and in 19 control patients with metastatic renal cell carcinoma receiving a similar immunotherapy regimen. The serum S100B level was elevated in 81% of the patients before treatment. Marker levels were significantly higher in patients who did not respond (n = 22). Patients with S100B levels ≥ 1.0 μg/l were less likely to obtain remission or stable disease than the group with normal or moderately elevated serum concentrations (P< 0.01). After treatment, 17 of the 31 (55%) patients with stable or responsive disease had a S100B serum level below the cut-off point versus only one of the 22 (5%) patients in the group with progressive disease. For LDH the proportions of patients were 17 out of 31 (55%) and nine out of 22 (41%), respectively. In 15 melanoma patients there was a transient rise in the level of serum S100B at the beginning of systemic therapy. All 19 patients in the control group had an initial serum S100B level ≤ 0.16 μg/l, but nine showed a transient rise during immunotherapy. In conclusion, S100B levels are of value for predicting the response to and for monitoring patients during chemoimmunotherapy.