Alpha IIb beta 3 (GPIIb-IIIa), the platelet receptor for fibrinogen, is a member of the integrin superfamily. We have now cloned the mouse and rat beta 3 cDNAs. These data represent the first available non-human beta 3 sequences, allowing important comparative analyses. Both beta 3 sequences are highly homologous with human beta 3, well above average rodent-human protein homology of 79%. The ligand binding domains (aa) 109-171 and 204-229) are, respectively, 90% and 100% homologous. The beta 3 transmembrane and the cytoplasmic tail are surprisingly highly conserved, being 97% and 100% homologous, respectively, but share little homology with beta 1, or beta 2. This latter difference argues strongly in favor for a crucial beta 3-specific function for these domains. In conclusion, we present the first comparative analysis of beta 3 chains and demonstrate high overall homology. The biological implications of these comparisons are discussed.