Sixty-six consecutive patients who underwent curative resection for rectal cancer were studied prospectively to evaluate the roles of sequential carcinoembryonic antigen (CEA), tissue plasminogen activator (TPA), and carcinomatous antigen 19-9 (Ca 19-9) determinations in the early diagnosis of resectable recurrences. Thirty-three recurrences were detected between 6 and 42 months. CEA, TPA, and Ca 19-9 showed a sensitivity of 72.7 percent, 78.8 percent, and 60.1 percent, respectively, and a specificity of 60.6 percent, 60.6 percent, and 87.9 percent, respectively. In 23 cases the rise in the value of CEA and/or TPA and/or Ca 19-9 was the first sign of recurrences, and the diagnosis was established later by clinical methods. In this group, the lead time was two months for liver metastases and four months for disseminated metastases. As far as the relationship between localization of recurrence and marker level increase is concerned, of 16 hepatic metastases CEA, TPA, and Ca 19-9 showed a sensitivity of 94 percent (P less than 0.05), 69 percent, and 62 percent, respectively. Of six patients with local recurrences, CEA, TPA, and Ca 19-9 showed a sensitivity of 50 percent, 100 percent (P less than 0.05), and 83.3 percent, respectively. Of three patients with peritoneal carcinomatosis, CEA, TPA (P less than 0.05), and Ca 19-9 showed a sensitivity of 0 percent, 100 percent, and 0 percent, respectively. No significant differences were reported among the three markers according to multiple metastases and metachronous polyps. Fourteen patients (42.4 percent) underwent surgical treatment for recurrent disease, and eight of them (57 percent) showed a resectable disease, for a total resectability rate of 24.2 percent. The findings of our study indicate that a follow-up program based on CEA, TPA, and Ca 19-9 assays is related to an early diagnosis and a good resectability rate for both local and metastatic recurrences from rectal cancer.