BACKGROUND Troglitazone (Rezulin) is a promising new oral hypoglycemic agent recently approved by the Federal Drug Administration for use in type II diabetes mellitus. Although troglitazone is not metabolized by the cytochrome p450 3A isozyme family, it is a potential inducer of this system. Other medications, e.g., rifampin and phenobarbital, which also induce p450 3A activity, have been reported to significantly decrease cyclosporine (CsA) concentrations. METHODS We report a case of a stable renal transplant patient who had a decrease in CsA concentration after beginning troglitazone and who subsequently developed an acute rejection episode. We then reviewed all stable renal patients begun on troglitazone over the previous 6 months. RESULTS The seven transplant patients who had been started on troglitazone therapy experienced a statistically and clinically significant decrease in CsA 12-hr trough levels immediately after the institution of troglitazone therapy. CONCLUSIONS A potential interaction exists between troglitazone and CsA. Transplant patients on CsA who receive troglitazone therapy should be monitored closely.