The present invention relates to TNF-.alpha. binding molecules and nucleic acid sequences encoding TNF-.alpha. binding molecules. In particular, the present invention relates to TNF-.alpha. binding molecules with a high binding affinity, a high association rate, a low dissociation rate with regard to human TNF-.alpha. and that are capable of neutralizing TNF-.alpha. at low concentrations. Preferably, the TNF-.alpha. binding molecules of the present invention comprise light and/or heavy chain variable regions with fully human frameworks (e.g. human germline frameworks).