One of the principal applications of tumour markers is the early detection of recurrent disease in the follow-up of patients. In the study described here, we compared the usefulness of two serum markers for melanoma, 5-S-cysteinyldopa (5-S-CD) and melanoma inhibitory activity (MIA), in the monitoring of postsurgical melanoma patients. A total of 154 serum samples taken from 45 melanoma patients, who underwent surgery of the primary tumour and were under periodical follow-up for 13 to 180 months, were analysed. Serum MIA measurements were performed using an enzyme-linked immunosorbent assay (ELISA), and 5-S-CD levels were determined using high performance liquid chromatography (HPLC). In 72 serum samples taken from a group of 31 non-progressive patients with a median follow-up of 48.5 months, false positive rates of both markers were equally low, being 6.9% (five out of 72) for 5-S-CD and 8.3% (six out of 72) for MIA. In contrast, the sensitivity of MIA at the time point of the first clinical relapse in 14 progressive patients was significantly greater than that of 5-S-CD (0.64 [nine out of 14] versus 0.21 [three out of 14]; P < 0.05). Furthermore, seven patients showed abnormal serum MIA values 4-53 months prior to the clinical detection of metastasis, and the elevated levels were often noted on multiple occasions. These results show that MIA was superior to 5-S-CD in monitoring melanoma patients under periodical follow-up after the primary surgery. Repeated elevation of serum MIA levels may predict the presence of clinically undetectable occult metastases, which warrants further prospective investigations to assess the prognostic significance of serum MIA levels in postsurgical melanoma patients.