Synthetic antibody libraries are constructed using designed synthetic DNA that facilitates the use of highly optimized human frameworks and enables the introduction of defined chemical diversity at positions that are most likely to contribute to antigen recognition. Using a relatively simple design based on a single human framework into which diversity is restricted to four complementarity-determining regions and two amino acids (tyrosine and serine), these synthetic antibody libraries are capable of generating specific antibodies against a diverse range of protein antigens. Moreover, by using the methods described here, more complex libraries can be constructed that are able to produce synthetic antibodies with affinities and specificities beyond the capacity of natural antibodies. Since these methods rely entirely upon standard supplies, equipment, and methods, construction of such libraries can be performed by any molecular biology laboratory.