Pruritus has been a side effect, associated with several biologic response modifiers, most commonly interferons and interleukins. Reports of pruritus are anecdotal and have not been a focus of attention. Itch fibers are essentially pain fibers, and gabapentin is used for neuropathic pain. This has led to our formal investigation of gabapentin for interleukin-2 (IL-2)-related pruritus. Clinical records of 54 patients treated with high-dose IL-2 from January 2005 to December 2006 were reviewed. Among 30 patients, who complained of pruritus, 17 patients were given gabapentin. These 17 patients were interviewed using a specific IRB approved questionnaire, which quantified pruritus according to CTCAE v3.0 criteria. According to CTCAE scale, the mean pruritus before gabapentin was 2.41, which decreased to 0.65 after gabapentin treatment and was statistically significant (P<0.0005). IL-2 therapy is frequently associated with varying degrees of peripheral eosinophilia. Relationship between pruritus and the degree of eosinophilia was also analyzed. Patients grouped into mild eosinophilia (eosinophil count<1500/mL) and moderate to severe eosinophilia (eosinophil count>1500/mL) during HDIL-2 therapy was evaluated for pruritus. χ² test for independence of variable between degree of eosinophilia and pruritus was 0.714 with no statistically significant correlation. To summarize, gabapentin is used in our facility with excellent response against pruritus. Hypothesizing the likely mechanism of pruritus in patients treated with IL-2, we suggest that gabapentin should be considered an effective and safe treatment in IL-2-related pruritus, and this concept could be applied to pruritus encountered in similar clinical settings.