To elucidate the mechanisms of action of GnRH agonists on uterine leiomyomas, morphometric and ultrastructural studies have been carried out on leiomyomas from patients treated with goserelin, and comparisons made with untreated tumors. The treated cases showed a variable degree of reduction of uterine size associated with leiomyoma shrinkage, and there was a correlation between the volume loss and the original size of the uterus. The morphological features of the treated lesions were very variable, with some showing evidence of marked cellular shrinkage and ultrastructural cytoplasmic changes, some having a lymphoid cell infiltrate, and others being indistinguishable from untreated control cases apart from having an increased number of compound lysosomes in the myoma cell cytoplasm. The degree of cellular shrinkage, measured by nuclear crowding, showed an inverse relationship to the proportion of collagen in the sections but none of the histological variables measured correlated with the degree of uterine shrinkage. It is concluded that the proportion of collagen in the lesions and other factors such as density of estrogen receptors, vascularity, cell proliferation rates, and degree of inflammatory cell infiltration affect the response to GnRH agonist therapy.