Mechanisms to account for the unusual properties of a DR1αβ complex (designated DRgp50) that is resistant to dissociation under normal conditions utilized were investigated. Expression of this DRgp50 complex is highly correlated with the failure of cells from certain DR1 individuals (DR1x) to stimulate specific DR1-restricted or alloreactive T-cell clones. Pulse/chase experiments demonstrated that this DRgp50 complex was not detectable until approximately 1 h of chase. The DR1 α and β chains associated into the heterodimer in the absence of glycosylation and alterations in the number of oligosaccharides or sialylation of cell surface forms were not evident when compared with normal DR1 α and β chains. Restriction fragment length polymorphism patterns of DRβ genes from normal (DR1n) and DR1x individuals were indistinguishable. However, a difference in the α chain genes between DR1n and DR1x individuals was revealed using Bgl II. This Bgl II restriction site mapped to the 3′ untranslated region of DRα and represents a new genomic marker to distinguish this functional and biochemical variant of DR1. © 1988 Springer-Verlag.