Continuous exposure to naturally-derived chemotherapy agents such as etoposide may theoretically override drug resistance due to overexpression of the multidrug resistance gene product, p-glycoprotein. Dexamethasone in high dose may have a similar overriding effect. Data also suggest that ifosfamide both by continuous infusion and when combined with a platinum compound may be more effective. Forty-four chemotherapy-refractory/relapsed lymphoma patients received the DICE infusional regimen. The programme consisted of dexamethasone 40 mg i.v. daily for 4 days, ifosfamide 1500 mg mixed with equal dosing of mesna continuously infused i.v. daily for 4 days, cisplatin 25 mg i.v. each day for 4 days and etoposide 150 mg continuously infused i.v. daily for 4 days, all administered every 3 weeks. Doses of ifosfamide and etoposide were escalated by 250 mg and 25 mg, respectively, based on patient tolerance, usually lack of myelosuppression. Special hydration was not required. G-CSF support was provided to patients as required. All patients had disease that had relapsed from or was resistant to CHOP or a similar anthracycline-containing combination regimen. A majority had previously received at least two regimens and 27% had received three or more. Of 44 patients, 32 (73%) achieved a significant response consisting of 18 complete remissions (CR) (41%) and 14 (32%) partial remissions (PR). There were 81% objective responses in large cell lymphoma comprised of 50% CR and 31% PR. Previous response to chemotherapy predicted response to DICE: 83% (25/30) of prior responders vs 50% (7/14) of non-responders had a response to the treatment regimen (p = 0.031, Fisher's exact test). Patients not undergoing transplantation had a median time of 8 months on therapy and a mean of 10 months. Toxicity was haematological (36% developing grade III-IV toxicity) and neurological (9%). There were only three episodes of clinical cystitis or gross haematuria. Infusional DICE is an easily administered and well tolerated programme with significant activity in refractory or relapsed NHL and may be useful as a tumour-reductive therapy prior to high-dose chemotherapy and autologous stem cell transplantation.