Perifusion of dispersed female rat pituitary cells with medium containing 50 microM zinc acetate caused an acute, sustained and rapidly reversible inhibition of prolactin (Prl) secretion. This treatment had no influence on basal release of thyrotropin stimulating hormone (TSH), luteinizing hormone (LH) or growth hormone (GH). 50 microM Zn2+ also reversibly inhibited prolactin secretion stimulated by either 50 mM K+ or 10 nM TRH, but the secretion of GH, TSH and LH which was stimulated by 50 mM K+ or stimulation of TSH by 10 nM TRH was not inhibited. Thus zinc acts in a dynamic manner to selectively influence pituitary prolactin secretion.