The urinary excretion of the pheomelanin precursor 5-S-cysteinyldopa (5-S-CD) has been used as a tumour marker for metastatic melanoma. The eumelanin-related metabolite 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5M12C) is also excreted at high levels in some melanoma patients. In order to compare normal values, we measured urinary excretion and serum concentration of 5-S-CD and 6H5M12C in 33 Japanese normal subjects. The mean values of 5-S-CD and 6H5M12C in urine were 0.45 and 0.39 mumol/day, respectively, and those in serum 4.3 and 3.6 nmol/l. Levels of these markers in urine were much more variable than those in serum. We have adopted 1.5 mumol/day and 10 nmol/l as the upper limits for normal ranges of the urinary excretion and serum concentration, for both markers. No significant differences were found between men and women. There were no correlations among the four markers. The urinary excretion of both markers showed significant decrease in elderly subjects as compared with middle-aged subjects, while the serum concentration showed no age-dependent differences. These results suggest that the levels of 5-S-CD and 6H5M12C in serum are more reliable as tumour markers for the estimation of melanoma progression than those in urine.