OKT3 has become a commonly employed immunosuppressant for transplantation both as a prophylactic agent and as a means of reversing rejection. It was first thought to have few side effects associated with its use, but many findings have become recognized as manifestations of cytokine release. The severity of some CRS symptoms can be reduced by careful patient management. Strategies to moderate CRS show promise. The potential for use of nonactivating anti-CD3 antibodies may obviate the symptom complex entirely.