Considerable interpatient variability in steroid pharmacokinetics has been observed in renal transplant recipients. The purpose of this retrospective study is to evaluate the relationship between the dose of methylprednisolone (MP) used to treat acute rejection (AR) after renal transplantation and the response to treatment. 117 first AR episodes from 408 renal transplants were reviewed. The dose of MP used to treat AR was < 45 mg/kg/m2 in 60 patients and > and = 45 mg/kg/m2 in 57 patients. The correlation between fixed dose ( < 1.25 vs. > and = 1.25 g) and dose based on BMI was evaluated by simple linear regression analysis (r2 = 0.78, p < 0.0005). Response to treatment was as follows: MP successful (Group 1, n = 80); MP failed, OKT3 successful (Group 2, n = 17); MP and OKT3 failed (Group 3, n = 3) and MP failed, no further treatment (n = 17). No relationship was observed between the dose of MP, whether fixed or based on BMI, and (1) response to treatment of the first AR, (2) incidence of a second AR and (3) response to subsequent treatment with OKT3. Actuarial graft survival was higher in Group 1 compared to Group 2 (p < 0.0005), lower in Black recipients (p = 0.02) and higher when > and = 45 mg/kg/m2 of MP was used to treat AR (p = 0.06). In conclusion, no relationship between the dose of MP, whether fixed or based on BMI, and the response to treatment of AR was observed. MP dosage based on BMI may be a reasonable alternative to a fixed-dose regimen with the advantage of limiting steroid exposure and the consequent side-effects.