We examined immune and inflammatory activation during remission in patients with Crohn's disease who presented with various clinical profiles (prolonged remission vs. relapsing disease). Thirty-six patients with at least 3 years' follow-up starting from a remission period were studied retrospectively. Relapses were defined by a retrospective calculation of the Crohn's disease activity index or by the clinical judgement of the physicians in charge of the patients. Disease course over the study period was assessed by the mean number of annual relapses. Analysis used measurements during remission of the following: erythrocytes sedimentation rate, relative lymphocytosis, acid alpha1-glycoprotein, interleukin-6 (IL-6), and soluble interleukin-2 receptor (sIL-2R) serum levels. During the study period 21 patients experienced at least one relapse and 15 did not. Mean serum levels of sIL-2R and mean relative lymphocytosis in remission significantly discriminated between relapsing and nonrelapsing patients. Only the mean sIL-2R serum level was selected by multivariate analysis, with a cutoff value of 82 pM/1 (sensitivity of 76% and specificity of 80%). The only features correlated with mean number of annual relapses in the relapsing patients were mean serum levels of sIL-2R (r=0.58, P=0.015) and IL-6 in remission (r=0.45, P=0.039). Multivariate analysis demonstrated statistical significance only for the mean serum level of IL-6 (P=0.014). In Crohn's disease the persistent elevation in sIL-2R serum levels during remission corresponds to chronic active disease, while high serum levels of IL-6 in these patients is associated with a high frequency of relapse.