Epidermal growth factor (EGF) mRNA was quantified in samples of human myometrium, untreated leiomyomata, and leiomyomata from patients treated with a GnRH analog. Quantitative reverse transcriptase-polymerase chain reaction, using a synthetic internal standard, was applied to determine levels of EGF mRNA. In myometrium from uteri with no leiomyomata, levels of EGF mRNA did not differ between the proliferative and secretory phase of the cycle. Leiomyomata from women who had received no drug therapy had significantly higher amounts of EGF mRNA than myometrium from a normal uterus, but only in the secretory phase of the cycle. In the proliferative phase, leiomyomata did not have different amounts of EGF mRNA compared to normal myometrium. Untreated leiomyomata in the secretory phase of the cycle, but not those in the proliferative phase, had significantly more EGF mRNA than leiomyomata from women who had received treatment with a GnRH analog. These findings suggest that EGF is important in leiomyomata development, but imply that its production is only increased during the secretory phase of the cycle. This challenges the hypothesis that EGF production in leiomyomata is mediated by estrogen and raises the possibility that progesterone may be the more important hormone in fibroid growth.