Strategies to optimize the use of cyclosporin A (CSA) in renal transplant were analysed retrospectively. Based on the incidence of acute rejection during the first 15 days of transplant, oral dosing achieved adequate immunosuppression earlier than constant intravenous infusion of CSA. The lack of CSA blood monitoring and the use of different steroid doses in this period could be responsible for these conflicting results. The differential diagnosis between acute rejection (AR) and CSA nephrotoxicity (NX) during the first year of transplant was made based on clinical findings, CSA levels and histological evaluation. Therapeutic CSA concentration range between 200 and 400 ng/mL, using radioimmunoassay with polyclonal antibodies, and between 100 and 250 ng/mL, using specific monoclonal antibodies, were found. A correlation of r = 0.82 between these two methods were obtained in 122 simultaneous dosages. Histological abnormalities found in biopsies from patients with AR were not different from those obtained from patients with NX, before and after 90 days of transplant. The conclusion was drawn that the therapeutic CSA monitoring associated with histological evaluation can reduce the incidence of renal dysfunction and promote a long-term and stable graft survival.