LH-RH is a hypothalamic peptide that stimulates release of gonadotrophins from anterior pituitary, thus regulating reproductive functions. It has been assumed, usually with good reason, that D-amino acids with large aromatic side-chains must be present in position 6 of both LH-RH superagonists and antagonists for the highest levels of biological activity to be reached. However, using one of a recent generation of potent lH-RH inhibitory analogs as a model, we have found that the insertion of D-lysine or, better still, D-arginine in this position results in greater antiovulatory activity in the rat over corresponding D-phenylalanine6- and D-tryptophan6-analogs.