Various adjuvant therapy trials in high risk melanoma are at present ongoing in the world. Interferon-alpha (IFN-alpha) and ganglioside vaccines are currently being evaluated on both sides of the Atlantic Ocean. In Europe, the two largest randomized trials are being carried out by the EORTC Melanoma Cooperative Group. In patients with a moderate risk (about 35%) of having micrometastatic disease, EORTC trial 18961 will investigate placebo versus vaccination with the ganglioside GM2 vaccine (GM2-KLH/QS-21) in 1000 patients with stage IIA melanoma (T3N0M0). This trial will be started during spring 1997. In stage IIB-IIIB (T4N0M0-TxN1-2M0) patients with a very high risk (about 80%) of having micrometastatic disease, EORTC trial 18952 (1000 patients) will investigate placebo versus adjuvant therapy with high or low intermediate doses of IFN-alpha2b (10 MU subcutaneously every day, 5 days per week for 4 weeks, followed by either 10 MU subcutaneously, three times weekly for 1 year, or 5 MU subcutaneously, three times weekly for 2 years). This review will discuss the trials and the philosophy of the programme, which allows more toxic treatments to be investigated in patients with a very high risk, and only treatments with little or no toxicity to be evaluated in patients with only a modest risk of disease. Other recently completed and ongoing trials are also discussed. From all programmes it is clear that in the case of medical efficacy, the toxicity, impact on quality of life, and costs of the treatment determine whether a treatment will be accepted and implemented.