The purpose of this study was to evaluate the use of the acute-phase serum protein alpha(1)-antitrypsin (alpha(1)-AT) compared with the erythrocyte sedimentation rate (ESR), platelet count, and hemoglobin level in screening for inflammation in newly diagnosed and known patients with inflammatory bowel disease (IBD). The serum alpha(1)-AT level, ESR, platelet count, and hemoglobin values of 154 children who were initially evaluated for possible IBD, as well as of 113 children with known IBD, were compared to evaluate their value as markers of inflammatory activity. Of the 154 children evaluated for IBD, 103 did not have IBD, 28 were diagnosed with Crohn's disease (CD), and 23 were found to have ulcerative colitis (UC). The sensitivity and specificity for CD was for alpha(1)-AT, 100%, 92%; for ESR, 68%, 94%; and for UC was for alpha(1)-AT, 70%, 92%; for ESR, 61%, 94%. In the 113 children with known IBD (66 CD, 47 UC), the sensitivity and specificity for predicting disease activity was for CD for alpha(1)-AT, 94%, 59%; for ESR, 52%, 63%; and for UC was for alpha(1)-AT, 79%, 76%; and for ESR, 59%, 82%. The determination of serum alpha(1)-AT levels was more sensitive and specific than the ESR in the initial diagnosis of CD and in predicting subsequent disease activity in both CD and UC.