Background. Several investigators have shown that blood levels of interleuhin 6 (IL-6) correlate with the severity of illness in critically ill or injured patients. However; little is known about differential arterial and venous blood levels of the cytokine, especially across the lungs. Methods. We measured differences in IL-6 levels in pulmonary and systemic arterial blood and then documented the production or elimination of IL-6 by the lungs in 19 patients with severe illness. Prospective data were obtained from multiple, simultaneous systemic arterial (ART) and mixed venous (MV) blood samples that were drawn for IL-6 analysis from systemic arterial and pulmonary artery catheters in 7 patients awaiting vascular operation and in 12 trauma patients being treated in the intensive care Unit. Results. A lung disorder was present in 5 patients (pneumonia [n = 1], lung trauma [n = 4]) and absent in the remaining 14 patients. The following data were obtained (mean +/- SD) from the highest MVIL-6 levels (pg/mL) in each patient. In patients with a lung disorder (n = 5) compared with those with no disorder (n = 14), ARTIL-6 was 9309 +/- 12,521 versus 134 +/- 128 (P = .010), MV IL-6 was 5516 +/- 7420 versus 137 +/- 129 (P = .011), the absolute difference was 3793 +/- 5271 versus -3 +/- 15 (P = .011), and the percentage difference was 37.4% +/- 29.8% versus 1.5% +/- 12.3% (P = .001). The ART and MV IL-6 levels tended to be much higher in the 5 patients with pneumonia (n = 1) and lung injuries (n = 4) than in the patients without apparent pulmonary problems. In addition, the patients with a primary lung disorder demonstrated a net increase in IL-6 level 5 across the lungs, whereas there was no increase, but rather; a net reduction of IL-6 levels across the lungs in patients without a lung disorder Conclusions. The lung appears to be a major producer of IL-6 in patients with an inflammatory lung process. There is a 39% increase in the level of IL-6 as it passes through inflamed lung, producing a marked difference in ART and MV IL-6 levles. Normal lung demonstrated little effect on either ART or MV IL-6 levels.