To determine risk factors for small vessel disease after heart transplantation (HTx), characteristics of donors and organ harvesting were evaluated in 246 HTx patients (205 male, 41 female, mean survival 5.4 years). In right ventricular endomyocardial biopsies (EMB, n = 5421) evidence of microvascular disease [endothelial cell (EC) swelling/vessel wall thickening] was evaluated by light microscopy (hematoxylin and eosin staining, x 200). Mild EC swelling/vessel wall thickening were found in 204 and 213 patients, severe EC swelling/vessel wall thickening were present in 23 and 142 patients respectively. Evidences of mild and severe acute cellular rejection were found in 2064 and 421 EMB respectively. Microvascular disease was positively correlated with mild acute rejection episodes (P < 0.05). EC swelling was more frequent in patients with donors dying of craniocerebral trauma. No correlations were present to further demographical data. Microvascular alterations after HTx seem to be the result of an immunologic conflict rather than to depend on nonimmunologic factors.