Large plaque (LP) and small plaque (SP) variants of Infectious Bursal Disease Virus (IBDV) which are formed in vitro after serial passages in CE-cells at low or high multiplicities of infection were tested for their pathogenic properties in susceptible chickens. LP virus caused clinical manifestations and destruction of the Bursa of Fabricius (BF) without killing the animals. No signs of a disease appeared after infection with SP virus, and only limited necrotic foci developed in the BF. Coinfection with the SP variant and the highly pathogenic wild type (wt) virus reduced mortality and the severity of the disease. In contrast to the SP variant, which forms incomplete particles of low density, with one or the other of the two genomic RNA segments missing, the two RNA segments characteristic for IBDV were present in approximately equal amounts in wt particles with a buoyant density of 1.29 g/ml isolated from the BF. In spite of an almost total replacement of one of the two major structural polypeptides with a molecular weight of 32 kd by a 28 kd protein, infectivity in this low density fraction was only slightly reduced. This finding underlines the importance of the type of post-translational modification in lymphoid cells or fibroblasts.