The effects of the uterotrophic steroids, estradiol benzoate, testosterone propionate and progesterone, and their interaction with the estrogen antagonist, MER-25, and the androgen antagonist, A-norprogesterone, on uterine weight, histology and selected biochemical parameters were studied in immature rats. All 3 hormones increased uterine weight in a dose-response relationship, but only the estrogen induced accumulation of intraluminal fluid. These steroids also increased total uterine RNA and DNA and decreased DNA concentration. RNA concentration was not altered consistently. All these uterotrophic compounds increased glucose-6-phosphate dehydrogenase, TPN-isocitric dehydrogenase and TPN-malic enzyme activity ([mu]moles TPNH/min/mg DNA). Uterine water and nitrogen concentrations were unaltered by any treatment studied. The 3 hormones induced distinctive alterations in the histology of the immature rat uterus. MER-25 did not alter uterine weight, histology or any of the biochemical end-points studied, with the exception of a slight elevation in both total RNA and RNA concentration. It did, however, antagonize the estrogen-induced effects on uterine weight, morphology and biochemistry. At the higher dose levels, MER-25 partially reversed the uterotrophic effect of testosterone propionate and augmented the effects of progesterone on some of the parameters measured. A-norprogesterone partially inhibited the androgen-induced elevations in uterine weight, total RNA and TPN-malic enzyme acitvity and the alterations in histology. Progesterone, employed as an antagonist, was only slightly effective against estrogen and was additive, rather than antagonistic, to the uterotrophic effect of testosterone propionate.