A single-arm, phase II perspective clinical trial was done in a tertiary care setting to determine the efficacy of high-dose methylprednisolone in the treatment of patients with refractory or relapsed multiple myeloma. Twenty patients who had failed at least one chemotherapeutic regimen received methylprednisolone (2 g) intravenously three times weekly for 8 weeks. After 8 weeks, responders were placed on a maintenance phase of 2 g intravenously weekly with an 8-week reinduction at the time of relapse. Five patients died within the first month of therapy. There were two complete responses, two objective responses and three minor responses. The median survival for all 20 patients was 2.2 months. Median survival for the seven responders was 19 months, with a relapse-free survival of 15 months. Five patients survived at least 16 months. High-dose methylprednisolone is an easily administered, relatively nontoxic, and effective therapy in a subset of patients with multiple myeloma.