In a prospective study of 622 women with breast cancer, those with one to three histologically positive axillary lymph nodes were randomised after mastectomy to receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2 intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 28 days for six cycles (CMF × six), or for twelve cycles of the same chemotherapy (CMF × 12). Those with ≥ four positive nodes were randomised to one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy (RT) followed by six cycles of the same chemotherapy (RT + CMF × six). With about 10 years median follow-up, there was no significant difference in survival or disease-free survival among the three groups. There was evidence of decreased locoregional recurrence in patients with ≥ four nodes who received RT + CMF × six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the presence of ≥ four positive nodes (negatively) and the percentage of ideal (full) dose of CMF received (positively) were the strongest factors predictive of survival. This study shows no advantage for 12 over six cycles of CMF chemotherapy in women with breast cancer and positive axillary nodes. There was a suggestion of decreased locoregional recurrence but no improvement in survival with radiotherapy for women with ≥ four positive nodes. © 1992.