Despite frequent use of intravenous (i.v.) cyclosporin A (CsA) in the early post-operative course of transplant recipients, allergic reactions have been infrequently described. Of 134 transplants, we report four pediatric renal transplant recipients with severe reaction to i.v. CsA with pulmonary capillary leak syndrome. Pulmonary edema developed at a mean time of 3.5 h after commencement of i.v. CsA, with two patients requiring mechanical ventilation. Discontinuation of i.v. CsA and conversion to oral CsA was followed by rapid resolution of pulmonary edema, suggesting that cremaphor, the solubilizing agent in the i.v. formulation, is likely to be responsible for this adverse response. Skin prick testing with cremaphor was negative in all patients and alternative mechanisms for the cremaphor response are proposed. It is likely that inadequate mixing of the i.v. CsA solution triggered this reaction, by delivering a higher concentration of cremaphor at the start of the CsA infusion. Pulmonary edema in the early post-transplant course in the absence of obvious fluid overload should prompt the diagnosis of an i.v. CsA reaction. This life-threatening reaction is easily reversible if recognized, and can be managed easily without compromise to the allograft, by discontinuing i.v. CsA and switching early to an oral CsA formulation.