The GATA-1 transcription factor has been shown to be important in the regulation of globin and non-globin genes in erythroid, megakaryocytic and mast cell lineages. It is a member of a family of GATA proteins which both overlap in their expression patterns and bind the motif (A/T)GATA(A/G). The GATA family of proteins are also members of the superfamily of zinc finger-like domain proteins and have two similar domains of the type Cys-X2-Cys-X17-Cys-X2-Cys which direct the DNA binding of the protein. A random oligonucleotide selection procedure has been employed to further elucidate the mechanism of GATA-1-DNA recognition. The resulting oligonucleotides were tested for binding activity to both wild-type and mutant GATA-1 proteins. Two classes of GATA-1-DNA interaction have been defined, the first requiring only the carboxy finger of GATA-1 to bind and having the motif GAT(A/T), the second requiring both finger domains to bind and having the core motif (T/C)AAG. By using sequence comparison and depurination analysis it is concluded that the two finger-like domains of GATA-1 have different DNA binding recognition motifs. Binding of GATA-1 to GAT(A/T) motifs is associated with transcriptional activation of linked genes. The only known (T/C)AAG motif is in the distal CAAT-box promoter region of the human A gamma-globin gene where the binding of GATA-1 appears to regulate the correct developmental suppression of gamma-globin expression.