The specification provides methods of preparing high-affinity antibodies to a macrophage migration inhibitory factor (MIF) in animals in which the MIF gene has been homozygously knocked-out (MIF.sup.-/-). Also provided are methods of preparing hybridomas which produce the anti-MIF antibodies, methods of administering the antibodies to treat inflammatory or cancerous conditions and/or diseases modulated by MIF, as well as compositions comprising said high-affinity anti-MIF antibodies.