The purpose of this pilot study was to describe short- and long-term changes in cognitive function and quality of life in patients with melanoma receiving interferon (IFN) alpha-2b. This study used a three-group, repeated measures design in which cognitive function and quality of life were evaluated prior to initiation of treatment at 3-month intervals during treatment and 3 months following the completion of treatment. The sample consisted of 16 adults with Stage II or III melanoma, randomized to one of three treatment groups. Participants in Arm A received high-dose IFN alpha-2b, those in Arm B received low-dose IFN alpha-2b, and those in Arm C received no therapy (control). No significant changes in cognitive function were detected. In participants in Arm A, there was a significant deterioration in the physical well-being dimension of quality of life from baseline to 3 months after beginning therapy.