Thyrotropin-releasing hormone (TRH) is a well-known regulatory factor of prolactin (PRL) secretion and synthesis in lactotrophs. Recently we have found that TRH stimulates early tyrosine phosphorylation of MAP kinase in GH3 cells. Then we investigated whether tyrosine phosphorylation in TRH action is involved in TRH-stimulated PRL secretion by GH3 cells, using a 4-hydroxycinnamamide derivative (ST638), a tyrosine kinase inhibitor. TRH-stimulated tyrosine phosphorylation of MAP kinase and PRL secretion were remarkably inhibited by ST638 treatment. These results suggest that tyrosine phosphorylation of MAP kinase is strongly associated with TRH-stimulated PRL secretion.