To assess the effects of postoperative radiation therapy and chemotherapy on tumor recurrence and patient survival, 227 patients (data on 202 of whom were analyzed) who had undergone "curative" surgical resection for rectal adenocarcinoma were prospectively and randomly assigned to one of four treatments: no adjuvant therapy (concurrent controls, 58 patients), postoperative radiotherapy with 4000 or 4800 rad (50 patients), postoperative chemotherapy (fluorouracil and semustine [methyl-CCNU], 48 patients), or a combination of radiation therapy and chemotherapy (46 patients). Five years after the entry of the last patient and with a median follow-up of all survivors for 80 months, the recurrence rate was highest among the control patients (55 per cent) and lowest among the patients receiving a combination of adjuvant radiation and chemotherapy (33 per cent). Time to tumor recurrence differed significantly among the four treatment groups (P less than 0.04); it was significantly prolonged by combined radiation and chemotherapy as compared with resection alone (P less than 0.009). Overall survival did not differ significantly among the treatment groups. The superiority of the combined-modality regimen appeared to be attributable to the effects of radiation therapy and chemotherapy in controlling local and distant recurrences, respectively. We conclude that this study provides evidence supporting the use of postoperative radiation therapy in conjunction with chemotherapy in patients who have had "curative" resection of rectal cancer with involvement of perirectal fat or regional nodes or both (Stages B2 and C).