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Currently there are no completely reliable methods for predicting an impending relapse in Crohn's disease. As ~50% of patients in remission [Crohn's disease activity index (CDAI) < 150] show some laboratory abnormalities, we inquired whether these alterations might be of value for predicting relapse. We prospectively studied 41 patients with Crohn's disease who had been showing CD AI < 150 for at least 6 mo before entering the study and who were not receiving any long-term treatment. The 41 patients were studied at the ninth and at the 18th month after inclusion in the study. Disease activity was monitored by CDAI calculation and by measurement of erythrocyte sedimentation rate, white blood cell count, hemoglobin, albumin, α2-globulin, serum iron, C-reactive protein, α1-glycoprotein, and α2-antitrypsin. Seventeen of the 41 patients had a clinical relapse during follow-up. At the beginning of the study the patients who later relapsed showed a remarkable alteration of acid ai-glycoprotein (p < 0.0001), α2-globulin (p < 0.0003), and erythrocyte sedimentation rate (p < 0.0006), in comparison with the patients who remained in remission. By discriminant analysis a prognostic index with these laboratory investigations provided a high percentage (88%) of accuracy according to the outcome at the 18th month.