IL-15, a novel growth factor made by a variety of cells, stimulates T cell proliferation in a fashion similar to IL-2, IL-2 transcripts are not routinely found in rejecting human renal allografts at the time of clinically evident rejection. However, T cell proliferation continues as the rejection progresses. We postulated that IL-15 may be actively transcribed during clinical rejection and account, at least in part, for the ongoing T cell expansion. RNA was extracted from renal biopsies and reverse transcribed to cDNA which was used as template for competitive PCR. IL-2 mRNA was detected in just 3 of the 45 biopsy samples. IL-15 transcripts were detected in all renal biopsy specimens and was significantly increased in specimens obtained from rejecting as compared with nonrejecting renal allografts. IL-15 transcription correlates with rejection and may play an important role in T cell mediated rejection.