Inhalation of swine dust induces airway inflammation and general symptoms, such as fever and malaise. In the present investigation, the presence and time course of changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in serum were studied to evaluate possible mechanisms by which inhalation of swine dust induces general symptoms. A group of 14 previously nonexposed subjects weighed swine for 3 h. The average +/- SD inhalable dust concentration was 22.4 +/- 4.7 mg/m3 and endotoxin, 1.2 +/- 0.4 microgram/m3. TNF-alpha in serum increased from 2.5 (1.8 to 3.1) ng/L (median, interquartile range) before exposure to maximum values 10.0 (4.6 to 15.7) ng/L between 3 and 5 h after the start of exposure. IL-6 increased from less than 1.5 to 21.4 (18.6 to 33.6) ng/L 4 to 11 h after the start of exposure. Maximum IL-6 occurred 1 to 5 h after the maximum TNF-alpha. In many subjects, however, an early rise in IL-6 parallel to the change in TNF-alpha was seen. The results that some of the peripheral reactions to swine dust might be mediated by TNF-alpha and IL-6. The early rise in IL-6 implies multiple origins of the IL-6.