C4d deposition in the walls of peritubular capillaries is considered the key phenomenon in the histopathological diagnosis of humoral, i.e. antibody-mediated, allograft rejection. We have earlier proposed that deposition of C3c in glomerular capillaries and simultaneous intravascular accumulation of macrophages in allografts with immediate or early humoral rejection indicates a potentially serious condition with very poor prognosis. The clinical outcome of 45 cadaveric grafts with this phenomenon among 1960 renal allografts transplanted at our centre during 1984-1999, and the recipients of the contralateral kidneys, was retrospectively evaluated. Graft failure occurred in 44/45 grafts within 3 weeks, with graft loss in 33/45 (77%) within 4 months and 37/45 (82%) within 1 year. From the contralateral kidneys, 5/33 (15%) were lost within 1 year. In a recent series of early biopsies, we recognised that of 13 cases showing C4d positivity in peritubular capillaries but lacking C3c in glomeruli, 10/13 (77%) were still functioning after 4 months. The mean number of CD68(+) macrophages per glomerular profile, i.e. the glomerular macrophage index, shows a significant difference between C4d(+)C3c(-) and C4d(+)C3c(+) cases (p<0.001). Our results indicate the existence of a clinically important subgroup of early humoral rejection with particular morphological features.