To evaluate whether serum gamma-enolase is a useful marker for renal cell carcinoma alpha and gamma-enolases in tissues of 36 renal cell carcinomas and 13 normal kidneys, and in sera of 103 renal cell carcinoma patients were determined with an enzyme immunoassay system. Tissue gamma and alpha-enolase levels were 34 and 2.3 times higher, respectively, in renal cell carcinoma than in normal renal cortex. The tissue gamma enolase-to-total enolase value of renal cell carcinoma (5.3 per cent) was significantly higher than that of normal cortex (0.29 per cent) and medulla (0.51 per cent). Over-all serum gamma-enolase levels were elevated (more than 6.0 ng. per ml.) in 53 of 103 patients (51 per cent) with renal cell carcinoma. In regard to stage the positive rates were 34 per cent (12 of 35) of patients with stage I, 22 per cent (2 of 9) with stage II, 80 per cent (12 of 15) with stage III, 61 per cent (22 of 36) with stage IV and 61 per cent (5 of 8) with recurrent disease. The mean value of serum gamma-enolase in renal cell carcinoma (8.0 +/- 5.7 ng. per ml.) was significantly higher than that of normal subjects (3.1 +/- 0.9 ng. per ml., p less than 0.001). The mean value of serum gamma-enolase in patients with high stage tumors (III and IV, 9.9 +/- 6.8 ng. per nl.) was significantly higher than that of low stage tumors (I and II, 5.8 +/- 3.0 ng. per ml., p less than 0.001). In 39 patients treated by complete surgical excision serum gamma-enolase was significantly reduced postoperatively (p less than 0.01). Furthermore, 7 of 8 patients whose serum gamma-enolase levels were determined serially had levels within the normal range postoperatively that increased when distant metastases appeared. These results indicate that serum gamma-enolase could be a useful tumor marker to stage disease and monitor treatment in patients with renal cell carcinoma.