The purpose of this paper is to familiarise intensive care staff with the concept of isolated limb perfusion with recombinant human tumour necrosis factor alpha (r-TNF-α), a new modality in cancer treatment, which has attracted considerable attention. The systemic toxicity of this type of treatment, and of cancer therapy with r-TNF-α in general, is reviewed. This review is based on Phase I and Phase II trials published in the English language, along with supportive documentation and data on 64 patients treated with r-TNF-α in our own institution. Guidelines are offered for the successful management of this type of patient. Treatment with r-TNF-α results in a characteristic clinical syndrome, which resembles the sepsis syndrome with hypotension and respiratory failure being the main features. Toxicity is largely independent of the route of administration. Very high serum concentrations of TNF-α, if shortlived, can be less toxic than sustained low serum concentrations. Treatment of patients who have undergone isolated limb perfusion with high-dose r-TNF-α is feasible and effective in a modern intensive care unit (ICU) setting, even if high serum concentrations of TNF-α, due to leakage from the perfusion circuit, cannot be avoided. Most patients can be discharged from the ICU within 24 hours.