Libraries of the zinc finger DNA binding protein, Zif268, have been constructed and selected for affinity and specificity toward DNA targets using the phage display technique (Wu et al., 1995). Mutant proteins were purified to homogeneity and were characterized for their ability to interact with their DNA targets using a real-time biomolecular interaction assay (BIA). One mutant protein, C7, bound the Zif268 consensus binding sequence with a 13-fold increase in affinity as compared to the wild-type Zif268 protein. Mutant proteins with moderate affinity for new DNA targets within a consensus sequence of HIV-1 have also been obtained. Surface plasmon resonance based BIA has provided invaluable kinetic information which offers insights into the mechanism of protein-DNA interactions.