L-Arginine has been shown, in human breast cancers, to increase protein synthesis and the number of cells in the growth phase of the cell cycle. L-Arginine, therefore, may potentiate the response of breast cancers to cell cycle-specific cytotoxic agents. This phase II pilot study assessed the clinical, radiological and pathological responses in 44 patients with breast cancers > 4 cm in diameter (46 tumours: T2, n = 6; T3, n = 22; T4, n = 19), who received oral L-arginine 30 g day-1 for 3 days prior to each cycle of CHOP chemotherapy, followed after 4-6 cycles by radiotherapy. Following this treatment, 95% of patients had a clinical response: Complete response in 30% and partial response in 65%. Imaging, ultrasound and mammography revealed response rates of 91% and 76% respectively. Surgery was performed in 43 patients. Histological examination revealed that in 18% of cases there was no residual evidence of tumour. Furthermore, if residual tumour was identified, the degree of destruction was graded as ‘severe’ in 36% and ‘moderate’ in 30% of cases. Further studies are now required to evaluate the potential beneficial use of nutritional pharmacology in combination with existing treatment regimens.