As commonly used, adjuvant paclitaxel after doxorubicin in high-risk breast cancer patients results in a prolonged delay of the onset of radiation therapy after breast-conserving surgery. Concurrent delivery of breast irradiation with paclitaxel would allow for earlier initiation of radiation. We report on the toxicity of concurrent paclitaxel and breast irradiation after doxorubicin and cyclophosphamide. Twenty-four patients were treated with concurrent breast radiation and paclitaxel. All patients received four cycles of doxorubicin and cyclophosphamide followed by four cycles of paclitaxel, 175 mg/m2 every 3 weeks. The radiation therapy started after the first cycle in 3 patients, after the second cycle in 16, and after the third in 5. The breast received 4680-5040 cGy external beam irradiation, followed by a boost of 1000-2000 cGy. Fifteen patients received supraclavicular irradiation, and a posterior axillary supplement was used in five patients. Median follow-up after completion of irradiation was 11.5 months (range 2-29 months) with 21 patients followed >or=6 months, 12 followed >or=12 months, and 7 followed >or=18 months. Using Radiation Therapy Oncology Group (RTOG) acute toxicity scoring criteria, 7 patients experienced grade 1 skin and/or soft tissue reactions and 17 patients had grade 2 reactions. The average total duration of radiation treatment was 49 days (range 41-57 days). Only eight patients had radiation therapy interruptions for a median of 3.5 days (range 2-8 days): two more than 5 days. None had a chemotherapy dose reduction. One patient discontinued paclitaxel after the third cycle due to bilateral upper extremity neuropathy. No cases of pneumonitis or brachial plexopathy were seen. Concurrent treatment with every 3-week paclitaxel and breast irradiation was well tolerated. Additional study is needed to determine optimal timing, long-term toxicity, and potential benefits of concurrent radiation therapy and paclitaxel.