Pituitary hyperplasia as well as proliferation of the endometrium are typical responses to estrogen administration in rodents. Both insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) have been implicated as paracrine mediators and amplifiers of estrogen action in the rodent uterus. The auto/paracrine role of IGF-I, EGF, their receptors and IGF binding proteins in pituitary proliferation has not yet been solved. Here we have used a semi-quantitative reverse transcription polymerase chain reaction (RT PCR) assay to demonstrate the changes in IGF-I mRNA and EGF mRNA abundance in the proliferating male rat pituitary in response to estradiol benzoate (EB; 1 mg/kg b.w. twice weekly i.m. for 3 weeks) and modifying effect of drugs antagonizing the pituitary enlargement — antiestrogen tamoxifen (TAM, 5 mg/kg b.w. daily) and also the dopaminergic agonist terguride (TER, 0.66 mg/kg b.w. daily, routinely used for the treatment of prolactinomas). In three separate experiments, EB induced a 2.2-2.5 fold increase in pituitary weight. The abundance of IGF-I and EGF mRNAs in pituitaries of EB-treated animals did not differ from the controls in two experiments and in the third series with the most marked pituitary hyperplasia mRNAs of both growth factors were even significantly decreased. Antiestrogen TAM administered with EB partially blocked the EB-induced proliferation and significantly stimulated IGF-I mRNA (p = 0.003) and EGF mRNA (p = 0.023) expression, while EB or TAM alone did not stimulate mRNAs of the studied growth factors. Significant antiproliferative effect of dopaminergic agonist TER on EB-induced pituitary proliferation (p = 0.006) was accompanied with decreased IGF-I mRNA (p = 0.025), but not EGF mRNA abundance. Our results suggest that the estrogen-induced pituitary proliferation is independent of the local expression of IGF-I and EGF mRNAs.