Cardiopulmonary bypass may generate SIRS and subsequent multiple organ failure. Tissue damage is likely to arise from the untoward activity of infiltrating blood polymorphonuclear cells (PMNs) interacting with the endothelium of blood vessels to increase vascular permeability. The aim of this study was to determine the effect of leucodepletion in these patients, and to investigate whether leucofiltration of blood from SIRS patients modified the binding of PMNs to cultured endothelial cells. Twenty-four patients who met SIRS criteria at 36 h after cardiac surgery were equally randomized to leucofiltration (LF) or control therapy. LF patients (nine male; APACHE II 21 ± 2; age 62 ± 10) received 1 h filtration cycles using a venovenous extracorporeal circuit at 200 ml min−1, repeated at 12 h intervals. Control patients (12 male; APACHE II 21 ± 2; age 63 ± 9) received standard post-operative care. Hypoxaemia index (PaO2/FIO2) was calculated up to 96 h from the onset of treatment. Blood from patients with SIRS was also subjected to leucofiltration in a laboratory-based extracorporeal circuit and the PMNs examined for their ability to bind to monolayers of endothelial cells derived from human umbilical veins. The results are expressed as mean values ± SD. Patients undergoing leucofiltration received an average 4.2 cycles (range 1–8). After 15 min the total leucocyte count fell from 16.2 ± 5.3 to 10.4 ± 3.3, the PMNs from 14.4 ± 5.2 to 8.3 ± 4.2, and platelets from 127 ± 87 to 117 ± 82×109 litre. All of the counts returned to baseline values by the end of the 60 min filtration period. The average length of stay for the LF and control group was 206 ± 118 and 214 ± 196 h respectively. Four LF patients and three control patients died before hospital discharge. At 96 h, 2-way ANOVA showed that the hypoxaemia index was significantly improved in the LF group compared with control patients (P In conclusion, the present study demonstrates that leucofiltration safely removes circulating PMNs from patients with SIRS following cardiopulmonary bypass. The removal from SIRS blood of PMNs that adhere to endothelium could reduce the sequelae of events that underlie organ failure in this disorder, particularly as lung function of SIRS patients is improved by leucofiltration treatment.