Side effects of isolated limb perfusion (ILP) include rhabdomyolysis, paresthesia, or nerve palsy. The increase in intracompartmental pressure during ILP is thought to be linked to neuro- and muscular toxicity, and fasciotomy is recommended for protection. In 24 patients, intracompartmental pressure was measured. A flexible 5 F probe was placed into the non-tumour-bearing compartment of the perfused limb. Interstitial fluid pressure was measured using a piezoresistant tip. Compartmental pressure values were continuously recorded during and after ILP. The drugs used were a combination of doxorubicin, cisplatinum and melphalan or rhTNF-alpha combined with melphalan. The median overall compartmental pressure prior to ILP was 13 mmHg (range: 11-21 mmHg); during the heat-up phase the median pressure rose to 28 mmHg. During therapeutic perfusion a further increase could be documented and the maximum pressure measured was 90 mmHg; the median of the pressure maxima of all patients was 34 mmHg. During wash-out, at the end of the perfusion, a clear reduction in compartment pressures could be observed and the median dropped to a value of 27 mmHg. In all patients a continuous decrease in compartmental pressure could be recorded, reaching the pre-ILP values by 48 h post-operatively. A dramatic increase in compartmental pressure during ILP can be observed by continuous monitoring. Because of our observation that during the wash-out phase elevated compartmental pressures return to normal, there is no general indication for a fasciotomy. However, for patients maintaining a peak compartmental pressure above a critical threshold of 35 to 40 mmHg fasciotomy may be indicated.