Enhanced pro-inflammatory cytokine production is considered a pathogenic factor in non-alcoholic fatty liver disease (NAFLD). Peripheral blood production of interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) was studied in relation to the severity of histological changes of the liver in obese NAFLD patients. Basal levels in serum and production of IL-1alpha and TNF-alpha in peripheral blood cell cultures after stimulation with lipopolysaccharide (enzyme-linked immunoabsorbent assays) were measured in 11 patients with steatosis and 15 with steatohepatitis, who underwent gastrectomy with a gastro-jejunal anastomosis in roux and Y, and in 9 controls who underwent anti-reflux surgery. Production of IL-1alpha and TNF-alpha was 122 and 67% higher in patients with steatosis than control values, respectively. In patients with steatohepatitis, IL-1alpha production was 300 and 80% higher and that of TNF-alpha 110 and 26% higher, as compared with controls and steatosis patients, respectively. Production of IL-1alpha was positively correlated with that of TNF-alpha (r=0.78, p<0.0001). IL-1alpha and TNF-alpha production were both positively correlated with the degree of steatosis (r=0.68, p<0.001 and r=0.74, p<0.0001) and steatohepatitis (r=0.77 and r=0.75, p<0.0001) at liver biopsy, and with the homeostasis model assessment index (r=0.73, p<0.0001 and r=0.63, p<0.01), respectively. Basal serum IL-1alpha and TNF-alpha levels were comparable in the three groups studied. It is concluded that elevated production of IL-1alpha and TNF-alpha by in vitro stimulated whole blood cell cultures occurs in NAFLD obese patients, which might play a pathophysiological role upon inflammatory leukocyte infiltration of the liver.