The family of human cell surface heterodimers which includes VLA-1 and VLA-2 is now shown to include three additional heterodimers, here called VLA-3, VLA-4, and VLA-5. Each of these separate VLA structures is composed of a distinct alpha subunit (Mr 110,000-200,000 nonreduced) noncovalently associated with a common beta subunit (Mr 110,000 nonreduced). Chemical cross-linking experiments provided evidence that each VLA complex exists predominantly as a 1:1 alpha beta heterodimer. The VLA proteins are widely distributed, with one or more of the heterodimers present on nearly all cell types tested. Evidence for five distinct VLA alpha subunits was obtained from differences observed in antibody recognition, cell distribution patterns, two-dimensional gel analyses, and V8 protease cleavage patterns. On the other hand, the beta subunit present in each heterodimer was immunochemically and electrophoretically indistinguishable, and yielded identical V8 cleavage fragments. Immunoblotting experiments revealed that besides the Mr 110,000 beta normally seen, another beta protein was present that is smaller in size (Mr 90,000 nonreduced), altered or deficient in glycosylation, and not available for cell surface radiolabeling.