Routine antenatal prophylaxis with anti-D has become accepted as desirable, but concerns have been expressed about the adequacies of supply and safety of polyclonal anti-D. Human monoclonal anti-D has been produced using Epstein-Barr virus (EBV)-transformed peripheral B cells, sometimes coupled with fusions to myeloma cell lines. More recently, molecular biology techniques have been used to produce human monoclonal anti-D in a variety of different ways. Many monoclonal antibodies (mAbs) have been characterized for fine specificity and in vitro functional activity in International Workshops. Two mAbs have been shown to cause red cell clearance and immunosuppression in male volunteers. Considerations for the future development of monoclonal anti-D for prophylactic use are reviewed.