Increased capillary permeability is a central feature of the severe forms of haemorrhagic fever with renal syndrome (HFRS) and occurs also, though less frequently, in nephropathia epidemica (NE), one of the milder forms of this syndrome, caused by Puumala virus. We therefore searched for antiendothelial cell antibodies (AECA) in patients with NE and in those with other presumed or serologically proven acute viral illnesses. By enzyme immunoassay, using human umbilical vein endothelial cells (HUVEC) as the substrate, IgG class AECA were detected significantly more frequently in patients with NE and with influenza A than in Red Cross blood donors. A lesser degree of reactivity could be shown with a human alveolar cell carcinoma line and with human and mouse embryonic fibroblasts. Pretreatment of HUVEC with interferon-gamma (IFN-gamma), but not with IL-1 or tumour necrosis factor-alpha (TNF-alpha), increased their ability to bind IgG of sera from patients with NE and acute febrile illnesses. We conclude that, although AECA can be demonstrated in NE, they occur also in other acute viral illnesses and, unless cytopathic by a mechanism not shared by the AECA of these other illnesses, are unlikely to be casually related to the capillary leak in HFRS.