Combination chemotherapy including adriamycin is proving highly effective therapy for advanced breast carcinoma. This trial was designed to determine the response to and toxicity of a combination of cyclophosphamide, adriamycin and 5-fluorouracil (CAF). Twenty-six patients with metastatic breast carcinoma who had measurable sites of disease were evaluated. The over-all response rate was 62% being made up equally of complete (CR) and partial (PR) remittors. An additional 19% of patients had less than 50% tumour regression while only 19% had progressive disease. Patients with predominantly soft tissue or visceral metastases responded regularly to CAF, but bone metastases proved to be somewhat more resistant. Toxicity was not great; leucopenia was the most common manifestation, and no severe infections occurred during the trial. Cardiotoxicity occurred in one patient, who received more than 450 mg/m2 of adriamycin. The median time to relapse for responders (CR + PR) was 18 months. Responding patients have had a significantly longer survival than patients with progressive disease. Median survival time of responding patients (CR + PR) is not yet reached; 50% of the patients are still alive 30 months after commencing the trial, while, for patients with progressive disease, median survival time was only six months and none of the original five patients are alive. These and other reported results are sufficiently encouraging to warrant comparative evaluation of endocrine manipulation, combination chemotherapy, and both modalities concurrently, to define the optimal initial management for metastatic breast cancer.