Trials in high-risk melanoma patients evaluating the role of postoperative adjuvant treatment with interferons or other cytokines, ganglioside-based vaccines, or vaccines based on melanoma cells are ongoing or planned internationally. In Europe, the two largest randomised trials are carried out by the European Organization for Research and Treatment of Cancer-Melanoma Cooperative Group (EORTC-MCG). In stage IIA patients (T3N0M0) with a moderate risk of micrometastatic disease (35-40%), Trial 18,961 compares observation with ganglioside GM2 vaccination. This trial will be activated during the spring of 1998 and is expected to enrol 1000 patients. In stage IIB-IIIB (T4N0M0-TxN12M0) patients with a high risk of micrometastatic disease (approximately 80%), trial 18,952 compares observation with adjuvant therapy using two intermediate dosage regimens of interferon alfa-2b (IFN-alpha 2b). These trials and the philosophy of the EORTC-MCG programme allow more toxic treatment regimens to be investigated in patients with high-risk disease and only treatments with minimal toxicity to be evaluated in patients with moderate- to low-risk disease. Recently completed and other ongoing trials also are discussed. Overall, if clinical efficacy is demonstrated, the toxicity, impact on quality of life and treatment costs determine the acceptance and applicability of a treatment.