Crohn's disease (CD) and ulcerative colitis (UC) show an intestinal activation of T cells and macrophages within the inflamed lesions. The aim of the present prospective study was to determine whether circulating interleukins ( IL) represent useful markers of immune activation in vivo and to characterize their respective roles in monitoring disease activity. Serum concentrations of the soluble IL-2 receptor (sIL-2R), IL-6 and IL-1-beta were measured in 10 patients with CD and 10 patients with UC before, at day 10 and 2 years after resection of inflamed bowel segments. The data were correlated with neopterin, C-reactive protein and other standard parameters of disease activity. Preoperatively, mean sIL-2R concentration was 495 +/- 62 U/ml (mean +/- SEM; healthy controls: 210 +/- 25 U/ml; p < 0.02) in CD and 705 +/- 120 U/ml (p < 0.00002) in UC. The corresponding IL-6 serum concentrations were 37 +/- 6 U/ml in CD (controls: 11 +/-0.6 U/ml; p < 0.0036) and 33 +/- 6 U/ml (p < 0.04) in UC. Two years postoperatively, sIL-2R was still elevated in 6 out of 9 patients in both disease groups. These patients did not differ from the remaining group with respect to disease activity. Serum IL-6, elevated in 7 patients with CD and in 6 patients with UC at day 10 postoperatively, had returned to normal in all patients by this time. There was a significant correlation between sIL-2R and neopterin (r = 0.52; p < 0.02) and between IL-6 and C-reactive protein (r = 0.44; p < 0.05) but not between sIL-2R and C-reactive protein. The sensitivity of increased concentrations of sIL-2R and IL-6 to reflect active CD and UC is comparable to that of neopterin and C-reactive protein.