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Tacrolimus (FK 506 or Fujimycin) is an effective anti–T-cell agent derived from the fungus Streptomyces tsukubaensis. Some in vitro studies have demonstrated that the potency of tacrolimus can be up to 100 times to that of cyclosporine. Despite being a very potent immunosuppressant, its use is complicated by narrow therapeutic range, individual variation in pharmacokinetics, and a broad spectrum of drug interactions. We report a case of very high tacrolimus level (>120 ng/mL) in a patient who was on antiretroviral medication and tacrolimus. Despite having such high drug levels, patient's clinical presentation and course was benign. He was managed conservatively and this ordeal resulting in no long-term sequela.