Parenchymal microabscesses (MA) in liver transplant biopsies are frequently associated with cytomegalovirus (CMV) infection. However, other potential causes of MA have not been fully investigated. We studied additional etiologies for MA via histological evaluation and clinicopathological correlation. Three hundred seventy-two liver transplant biopsies from 97 patients (from 1991 to 1997) were reviewed and stained immunohistochemically for CMV. Numerous histological features were evaluated including size and number of MA, lobular and portal inflammation, and cholestasis. Medical records were reviewed for radiographic, laboratory, and other clinical data from the time of biopsy. The chi2 or Fisher's Exact test and ANOVA with adjusted multiple comparisons were used to determine statistical significance. Sixty-two of 372 biopsies (17%) from 43 patients contained MA. Biopsies were obtained between 4 days and 2.3 years posttransplant (median, 14 days). Nineteen percent of biopsies had CMV infection at the time of biopsy; 27% were associated with other bacterial, viral, or fungal infections; 10% had graft ischemia; 15% had biliary obstruction/cholangitis; 3% had a combination of ischemia and sepsis; and no explanation was found in 26% of biopsies. Numerous MA within a biopsy (>9) correlated with CMV infection (P <.005); no other histological features, including size of MA, correlated with the etiology of MA. Overall, 43 of 97 (44%) liver transplantation patients at our institution had biopsies demonstrating MA at some point in their posttransplantation course. CMV infection appears responsible for only a minority of cases. MA, although nonspecific, are an important histological finding in numerous conditions that may have a significant impact on both graft survival and overall patient morbidity.