Background. Hyperleptinaemia in chronic haemodialysis (CHD) patients has been associated with malnutrition, which is an independent predictor of morbidity and mortality in this patient group. Methods. To assess the influence of HD on plasma leptin, 10 CHD patients were crossover randomized to low-flux polysulfone (PS: F 6HPS), high-flux PS (F 60S), super-flux PS (F 500S) or super-flux cellulose-tri-acetate (CTA: Tricea 150G) for 12 weeks each. Blood samples were collected at the start of the study and each 12-week period. In addition, the relationship between patient characteristics, inflammation and leptin was analysed. Results. At baseline, all groups showed similar leptin concentrations (mean 33.6 ± 21.7 ng/ml). After a single HD session, a significant (P < 0.01) decrease was observed with all three high permeable devices (Tricea 150G -52.7 ± 6.4%; F 60S -63.1 ± 5.7%; F 500S -68.7 ± 8.2%), whereas leptin remained stable with low-flux PS. After 12 weeks, a marked increase was observed with low-flux PS (week 1, 30.4 ± 23.0; week 12, 40.5 ± 5.4 ng/ml, P = 0.05), no change with super-flux CTA and high-flux PS (Tricea 150G week 1, 29.4 ± 23.7; week 12, 32.0 ± 27.9 ng/ml, P = ns; F 60S week 1, 36.0 ± 31.8; week 12, 33.0 ± 31.2 ng/ml, P = ns), and a significant decrease with super-flux PS (week 1, 38.3 ± 33.0; week 12, 29.5 ± 31.9 ng/ml, P = 0.02). The change in leptin after 12 weeks was significantly different between super-flux PS, and both low-flux PS (P = 0.009) and super-flux CTA (P = 0.01). Besides interleukin-6 (IL-6) at the start of the study (P = 0.006), no correlations were observed between patient characteristics, parameters of inflammation and plasma leptin levels. Conclusions. Apart from low-flux PS, plasma leptin decreased considerably with all three high permeable dialysers after a single HD session. In the long run, leptin levels were lower with high-flux PS than with low-flux PS. Moreover, after switching from high-flux PS to super-flux PS (but not super-flux CTA), an additional decrease in leptin was observed. Apart from IL-6 at the start of the study, neither patient characteristics nor inflammatory parameters correlated with plasma leptin levels in this patient group.