The aim of this work is to reinvestigate the pentoxifylline (PTX) action on TNF alpha and IL-6 production using a whole blood ex-vivo model. 5 healthy controls, 2 septic patients (4 samples) and 3 patients in septic shock (7 samples) have been studied. Our data confirm the inhibitory action of PTX on TNF alpha production in healthy controls. This inhibition is nearly complete for a PTX concentration of 10(-3) M. More surprisingly a suppressive activity of PTX on IL-6 secretion has been found both in controls and septic patients. On the 7 samples of the 3 patients with septic shock no TNF alpha production has been detected. Taken altogether, these observations suggest a potential role for PTX as a modulator of the major cytokines involved in the pathogenesis of septic shock.