Leukocyte adhesion deficiency (LAD) is a heritable disease involving deficient expression of three related leukocyte adhesion glycoproteins: LFA-1, Mac-l, and p150, 95. These proteins ate a8 heterodimem containing identical 95,000 dalton 9 subunits. Here we demonstrate that the primary defect in LAD is in the 9 subunit gene. We identified five distinct (3 subunit phenotypes in LAD patients: undetectable (3 subunit mRNA and protein precursor; low levels of fi subunit mRNA and precursor; an aberrantly large 9 subunit precursor, probably due to an extra glycosylation site; an aberrantly small precursor; and a grossly normal precursor. Mutant 9 subunit precursors from LAD patients failed to associate with the LFA-1 a subunit. In family studies, inheritance of the aberrant precursors correlates with the known inheritance of the LAD defect.