Inflammatory bowel diseases lead to a systemic acute-phase response. Monocyte activation plays a central role during systemic acute-phase response via secretion of inflammatory cytokines. We determined the activation of peripheral-blood monocytes in patients with inflammatory bowel diseases by measuring their interleukin-6 (IL-6) secretion. Blood was obtained from patients with active Crohn’s disease before treatment [mean Crohn’s disease activity index (CDAI) = 332 ± 34] and from patients after treatment with prednisolone (mean CDAI index = 139 ± 20). The mean serum IL-6 levels measured by a hybridoma growth assay (B9) were 23 ± 4 U/ml before therapy and fell to 16 ± 3 U/ml after treatment with prednisolone. Healthy persons and patients with inactive Crohn’s disease usually had serum IL-6 levels below the detection limit of 4 U/ml. An ex vivo whole-blood system was used to measure IL-6 secretion by peripheral-blood monocytes with and without stimulation. Spontaneous IL-6 secretion in this system was about 9 U/ml in patients with Crohn’s disease and below the detection limit of 4 U/ml in healthy controls. Moderate stimulation of blood cells [100 pg/ml lipopolysaccharide (LPS)] from patients with active Crohn’s disease before and after treatment led to mean IL-6 concentrations of 1,160 ± 514 and 131 ± 54 U/ml, respectively. Maximal stimulation of peripheral blood before and after therapy by LPS (100 ng/ml) led to mean IL-6 concentrations of 5,570 ± 1,660 and 6,220 ± 1,630 U/ml, respectively. Thus, administration of glucocorticoids led to a rapid down-regulation of IL-6 synthesis by peripheral-blood monocytes. In conclusion, plasma IL-6 levels and spontaneous IL-6 synthesis in peripheral-blood monocytes are increased during active Crohn’s disease. After successful treatment IL-6 secretion by monocytes is strongly depressed. The maximal capacity of monocytes to synthesize IL-6 is not changed by active Crohn’s disease. Treatment with glucocorticoids may partially block the synthesis and secretion of IL-6.