The 56-amino-acid extension of GnRH in the human GnRH precursor (pHGnRH 14-69 or GAP) has previously been shown to inhibit PRL secretion from cultured rat pituitary cells. We have studied the effect of GAP and shorter sequences on prolactin secretion from human and rat pituitary cells. Bacterially synthesized GAP inhibited PRL secretion from human pituitary cells. At 10(-6) M GAP inhibition of prolactin release was 67.7% which was similar to that observed in rat pituitary cells (65.5%). A series of shorter peptide sequences (pHGnRH 14-26, pHGnRH 14-36, pHGnRH 14-37.NH2, pHGnRH 28-36, pHGnRH 38-49 and pHGnRH 51-66) which are potentially processed from GAP at basic amino acid residues had no effect on prolactin secretion from human or rat pituitary cells at doses up to 10(-5) M.