Hypocomplementaemic hereditary membranoproliferative glomerulonephritis (MPGN) type II is a common cause of the early loss of piglets in the Norwegian Yorkshire breed. The disease is associated with extensive complement activation due to a deficiency of factor H, a plasma protein which regulates complement. To investigate its mode of inheritance, 33 litters were bred from healthy animals associated with the disease, and a total of 385 recorded offspring were produced. The examination of renal tissue from the hypocomplementaemic piglets consistently revealed diagnostic signs of MPGN type II, including thickening of the glomerular capillary wall and proliferation of mesangial cells, dense intramembranous deposits, and massive glomerular deposits of complement component C3 and the terminal complement complex. No such glomerular lesions were detected in 20 normocomplementaemic littermates. The 88 affected piglets were present in 27 litters containing a total of 317 piglets, and there were approximately equal numbers of each sex. Retrospective immunoblot analysis and enzyme immunoassay of plasma samples from the MPGN-affected piglets and their healthy littermates revealed that the affected piglets were deficient in factor H, whereas the healthy piglets were not. It is concluded that porcine factor H deficiency is inherited as a simple autosomal recessive trait with complete penetrance, and consistently results in hypocomplementaemia and lethal membranoproliferative glomerulonephritis type II.