Objective: Acute antibody-mediated rejection requires specific treatment and has a negative impact on graft survival. The objectives were to report the incidence of antibody-mediated rejection after pancreas transplantation, the demographic data, the outcome and the pattern of C4d distribution, as well as the correlation with laboratory data. Methods: Optical microscopy, immunofluorescence for C4d staining and donor-specific antibody search by Luminex (R) in 31 kidney biopsies in 17 patients (median 87 days) and 34 pancreas biopsies in 22 patients (median 192 days), from August 2006 to August 2008. The following tests were performed:chi(2), t-Student, Pearson's correlation coefficient and logistic regression (p < 0.05). Results: Forty-seven percent of acute pancreas rejections were of humoral type: five acute; two subclinical and one silent. Before and after treatment of acute rejection (n = 17, 65% of biopsies): amylasuria 1271.3 +/- 1214.1 versus 1966.5 +/- 1423 U/h (p = 0.004); amylase 188.4 +/- 87.9 versus 102.3 +/- 47.2 U/l (p < 0.0001) and lipase 1219.1 +/- 594.4 versus 419.3 +/- 207.3 U/L (p < 0.0001), respectively. There was correlation between acute rejection diagnosis and amylase (p = 0.02) and lipase (p = 0.018), as well as correlation with each other (p = 0.0013, r(2) = 0.49). 27.3% of kidney acute rejections were of humoral type: one acute, one subclinical and one silent. There was no correlation between C4d staining and graft survivals. C4d pattern was diffuse in more than 60% of biopsies. Conclusions: antibody-mediated rejection after pancreas transplantation showed elevated rates, which suggests that C4d staining should be routinely investigated. Laboratory data may be a useful tool to diagnosis of acute rejection and to evaluate the response to treatment.