In the present study the effect of replacement of dietary fat by palm oil in the normal Western diet on the in vitro release of the inflammatory cytokines tumour necrosis factor (TNF), interleukin (IL)-6 andIL-8 was examined. A maximal replacement of 700 g/kg dietary fat was achieved for thirty-eight male volunteers who consumed either a palm-oil diet or a control diet in a double-blind, cross-over study with6-week experimental periods, and 3-week run-in and wash-out periods. At the end of both experimental periods, whole blood was stimulated in vitro with 0.02 (sub-optimal), or 10 ng lipopolysaccharide(LPS)/ml (maximal), whereafter TNF, IL-6, and IL-8 concentrations in the culture supernatant fraction were measured using specific enzyme-linked immunosorbent assays (ELISA). Mean cytokine production with sub-optimal, or maximal LPS stimulation of peripheral whole blood was similar for both the palm oil, and the control group. The relative TNF response, however, was reduced by replacement of dietary fat with palm oil. Separate analysis of the data from the first and second experimental periods strongly suggested that the residual effect of the palm-oil diet on the relative TNF response was longer than 9weeks. Cytokine homeostasis determines the course of the inflammatory response and the progression of atherosclerosis. The effect of palm-oil consumption on the proneness of the peripheral blood cells to produce TNF may, therefore, alter the prevalence of these common diseases.