We evaluated the toxicity and efficacy of the first palliative chemotherapy regimen after failure of high-dose chemotherapy in 148 patients with primary or metastatic breast cancer treated with high-dose chemotherapy (one full dose CTC (cyclophosphamide 6000 mg/m(2), thiotepa 480 mg/m(2), carboplatin 1600 mg/m(2)) or multiple courses CTC or 'tiny' CTC (tCTC) (two-thirds of the agents of the full-dose regimen), all divided over 4 days). After a median follow-up time of 46.8 (range 1-120) months, 79 patients had a relapse or progressive disease and 41 patients were treated with palliative chemotherapy. The most commonly used regimens were classical CMF (n=13), docetaxel (n=16) and less frequently anthracycline (n=4), paclitaxel (n=5), capecitabine (n=2) and vinorelbine (n=2). In both the CMF and docetaxel group, 3 patients required a dose reduction because of hematological toxicity. Objective responses were seen with CMF (23%) and docetaxel (69%) with a median duration of 161 (range 28481) and 196 (range 62-437) days, respectively. We found no relationship of toxicity and response with treatment free interval after high-dose chemotherapy. This report shows that conventional-dose palliative chemotherapy regimens may be safe and effective after failure of high-dose chemotherapy.