Recurrent/metastatic, undifferentiated nasopharyngeal carcinoma (UDNPC) is known to be chemosensitive but has rarely been studied in Phase II methodology. No studies concerning its chemoresponsiveness among southern Africans have been demonstrated to date. From 1990 through 1994, 18 African patients from the Johannesburg metropolitan area with recurrent (following radiotherapy failure) or primarily metastatic (bone) UDNPC were treated with ifosfamide (3 g/m), mesna, and cisplatin (50 mg/m) for 2 days. Three patients (15%) attained complete remission and eight (44%) partial remission, yielding an overall response rate of 59%. Median response duration was 28 weeks. Two patients (11%) had stable disease with symptomatic improvement and five (30%) progressed on therapy. Treatment was generally well tolerated but there was one treatment-related death (neutropenic sepsis). The combination of ifosfamide/cisplatin appears to be promising in UDNPC commonly seen in young patients in southern Africa. However, the duration of response still tends to be brief.