Thirteen patients with locally advanced or recurrent breast carcinoma were monitored during radiation therapy by multiple, sequential, fine-needle aspiration biopsies (FNAB) with flow cytometry. The material was analyzed for qualitative cytomorphological evidence of radiation effect and for DNA content and cell cycle alterations. DNA ploidy was not affected by the radiation therapy, although the aneuploid tumors showed an increased frequency of cell cycle alterations. The most common change seen was an increase in S-G2M (58%). Other changes included a decrease in the proliferative/growth fraction (17%) and no significant redistribution of cells (25%). There was a relationship between the initial proliferative activity of the tumors and the type of cell cycle change which occurred. Flow cytometric analysis was a better predictor of early clinical response than was cytomorphological assessment. Sequential FNAB with flow cytometry is an effective method of monitoring the response of breast cancer to radiation therapy.