BACKGROUND We have recently profiled inflammatory gene expression in acute appendicitis (AA) and identified a set of genes that are overexpressed in AA. The purpose of this study was to determine whether serum levels of a subset of proteins coded for by these overexpressed genes could differentiate patients with AA from those with other causes of abdominal pain and whether the serum levels of these proteins correlate with the histologic severity of appendicitis. METHODS Serum samples were obtained from a convenience sample of children between 1 and 21 y of age who presented to the emergency department (ED) with symptoms/signs of AA. Patients were assigned to the proven appendicitis (AA) or nonappendicitis (control) group based on histologic findings, chart review, and follow-up phone calls. The serum levels of haptoglobin, granulocyte colony stimulating factor (GCSF), interleukin 8 (IL-8), and C-reactive protein (CRP) were compared between groups. For patients with histologically proven appendicitis, a histologic severity score was assigned and correlated with the levels of potential serum biomarkers. RESULTS thirty-two patients were enrolled; 23 patients (72%) had AA. Serum levels of CRP and GCSF were significantly different between AA and control groups (7.0 versus 0.8, P=0.01 and 104.2 versus 58.7, P=0.03, respectively.) In patients with AA, there was significant correlation between GCSF serum levels and the appendicitis severity score [r=0.537, P=0.02]. CONCLUSIONS GCSF serum levels can distinguish between patients with AA and controls. GCSF may prove to be a useful adjunctive test in the diagnosis and staging of acute appendicitis.