We studied cellular proliferation by measuring the tritiated thymidine labeling index (TLI) in slices of primary invasive breast carcinomas. Estrogen receptor (ER) and progesterone receptor (PgR) were measured by ligand-binding assay. The TLI was a strong independent predictor of survival and relapse-free survival in women with or without axillary lymph nodal metastases and in American Joint Committee stage I. In operable node-negative women treated surgically, predicted survival at 5 years was 89 +/- 4% (probability +/- standard error) for 81 patients with low TLI (less than or equal to 3%), 64 +/- 7% for 101 with mid TLI (3.1-8%), and 66 +/- 6% for 86 with high TLI (greater than 8%) (P = 0.001). Probabilities of survival for patients with positive axillary nodes were 79 +/- 6% for 86 with low, 71 +/- 7% for 71 with mid, and 52 +/- 6% for 89 with high TLI (P = 0.0002). In stage I patients (tumor diameter not exceeding 2 cm), 5-year survival probabilities were 93 +/- 4% in 70 with low, 72 +/- 8% in 43 with mid, and 58 +/- 10% in 35 with high TLI, (P = 0.0005). The TLI was predictive for survival and relapse-free survival within subgroups positive and negative for ER and positive for PgR (P less than 0.05) in stage I patients, and a predictive trend was observed in the PgR-negative subgroup (P = 0.16). TLI also predicted within different categories of vascular invasion and nuclear grade. A stepwise Cox proportional hazards model selected TLI, number of positive axillary lymph nodes, and maximum diameter of the breast carcinoma as independent variables predictive of relapse, and added ER as a fourth variable for prediction of survival.