Serum and urinary concentrations of β<sub>2</sub>-microglobulin were measured for the first 21 days after renal transplantation to aid in diagnosis of acute rejection. Criteria developed after study of 15 patients were applied to the entire group of 31 consecutive cases. 29 instances meeting our criteria were identified in 651 days at risk and were associated with a mean maximal increase of serum creatinine of 74.8%. β<sub>2</sub>-Microglobulin methods may make possible detection of what is now subclinical rejection. β<sub>2</sub>-Microglobulin methods, however, are an adjunct to, not a replacement for classical methods for detecting acute rejection.