Sequential monitoring of peripheral T lymphocyte gene expression was performed in renal transplant recipients in the first 6 weeks following transplantation. The level of gene expression was correlated with clinical events, with emphasis on changes occurring during acute rejection. Forty-three renal transplant patients were monitored. Twenty-eight did not reject while 15 did. The most significant finding was that peripheral T cell IL-4, IL-5 and IL-13 gene expression increased at the time of acute rejection and decreased following successful anti-rejection therapy. While clear differences in the gene expression profiles between non-rejectors and rejectors were seen for IL-5 and IL-13, there were more similarities in the profiles between the two groups for IL-4. The increase in IL-5 and IL-13 expression in the rejectors prior to, and during acute rejection, and the subsequent return of both cytokines to their respective patterns for the non-rejectors, suggest that these 2 cytokines may be important markers of acute rejection. The similar decrease in IL-4 gene expression below its pre-transplant baseline in the first week following transplantation in both non-rejectors and rejectors before returning to the baseline, and a similar reduction in expression below the baseline following anti-rejection therapy before returning again to the pre-transplant levels suggest that IL-4 was more likely a sensitive marker of the changing level of immunosuppression rather than of the changes in alloreactivity. IL-4, IL-5 and IL-13 also had different gene expression profiles in the non-rejectors. Both IL-5 and IL-13 had a flat post-transplant gene expression profile, with IL-5 consistently below its pre-transplant baseline at all post-transplant time points while IL-13 remained at its baseline level throughout, IL-4 on the other hand had a variable profile, being below its baseline during the first week post-transplant before returning to its baseline subsequently. In contrast, IL-10 gene expression profile was totally opposite to that for IL-4, IL-5 and IL-13 in both non-rejectors and rejectors. In the non-rejectors, IL-10 gene expression was consistently above its pre-transplant baseline at all post-transplant time points.