Vascular endothelial growth factor (VEGF) messenger RNA (mRNA) and VEGF peptide were studied in human myometrium and leiomyomata. Amplification of complementary DNA from myometrium and leiomyomata by the polymerase chain reaction revealed three species of mRNA encoding VEGF: VEGF189, VEGF165, and VEGF121. In situ hybridization demonstrated VEGF mRNA expression throughout the smooth muscle cells of myometrium and leiomyomata. VEGF-like immunoreactivity was also detected in these tissues by immunocytochemistry. Quantification of VEGF mRNA using an RNAse protection assay demonstrated that in normal myometrium, levels of VEGF mRNA are significantly higher in the secretory phase than in the proliferative phase of the cycle. Leiomyomata did not have significantly different levels of VEGF mRNA compared with normal myometrium. In untreated leiomyomata, there was no significant difference between VEGF mRNA levels in the proliferative and secretory phases of the cycle. Leiomyomata from women treated with a GnRH anlog did not have significantly different levels of VEGF mRNA from untreated leiomyomata.