The recovery of prolactin (PRL) secretion following dopaminergic inhibition was studied in vitro using pituitary monolayer cultures. PRL secretion over 4 h was inhibited comparably by 10(-6) M dopamine (DA), 10(-7) M apomorphine (APO), and 10(-10) M bromocriptine (45%, 42%, 51%, respectively) with reciprocal increases in intracellular hormone content. After drug removal, the PRL secretion rate in the cultures that had been treated with DA was 208% of the control cultures by the 2nd h but returned to control values by 4 h, whereas the secretion rate after APO was 131-142% of control throughout the 4-h recovery period. In contrast, PRL secretion remained significantly less than control 20 h after the removal of bromocriptine. Although haloperidol (10(-7) M) prevented the inhibitory action of bromocriptine when added simultaneously, the addition of haloperidol did not restore PRL secretion when added in the posttreatment period. Thus, DA and APO inhibition of PRL release is readily reversible and is followed by early PRL hypersecretion. However, bromocriptine's effects are sustained and once started are not reversed by DA antagonists.