Chronic estrogen treatment results in elevated levels of the gelatinase pro-MMP-9 in the pituitary of tumor-susceptible Fischer 344 rats. In contrast, pituitary pro-MMP-9 level is not increased by estrogen treatment in rats of the tumor-resistant BN strain nor in rats of an F(1) hybrid of these strains. The gelatinase MMP-2 is also detected in rat pituitary, but its level is not affected by either estrogen or rat genotype. In 124 estrogen-treated rats from a backcross of the F(1) hybrid to the F344 strain, the levels of both monomer and dimer forms of pro-MMP-9 correlate with the tumor phenotypes mass, total DNA, and hemoglobin content of the pituitary. In this backcross, the QTL Edpm5 (_e_strogen-_d_ependent _p_ituitary _m_ass on Chromosome 5) has a significant effect on MMP-9 levels, with inheritance of the BN allele of Edpm5 correlating with suppression of estrogen-dependent MMP-9 expression.