Adenosine diphosphoribosyl transferase (ADPRT) activity was measured in endometrial nuclei isolated on estrus and day 4 from rats ovariectomized on estrus (day 0) and treated on days 0-3 with vehicle, estrone (E), progesterone (P), or E plus P, a treatment that supports a decidual response. Also, measures were made of ADPRT in endometrial nuclei isolated from rats during the estrous cycle, days 1-7 of pseudopregnancy, and days 5-7 of pseudopregnancy after decidual induction on day 4. E treatment produced an increase in ADPRT activity, DNA content, tissue mass, and total protein. P alone did not affect ADPRT activity or DNA content. Enzyme activity and DNA content measured after E plus P treatment were significantly lower than those after estrone treatment and higher than those in vehicle-treated controls. The parallel stimulation of ADPRT activity and DNA synthesis by E supports a role for ADPRT in cellular proliferation. The blockade of E-stimulated ADPRT activity by P is consistent with a previously proposed model of hormonal regulation of rat uterine pyridine nucleotide metabolism. In endometrium from cycling rats, ADPRT activity did not change between metestrus and proestrus, but declined on estrus. After a rise on day 1 of pseudopregnancy, ADPRT activity remained stable through day 5 and declined on day 6. The relatively constant enzyme activity during the cycle and early pseudopregnancy, when hormone levels undergo great changes, may reflect an additional level of control in intact animals not observed in ovariectomized hormone-treated rats. Decidual ADPRT activity declined on day 5, 1 day after uterine trauma, and increased on day 6. This pattern of enzyme activity is consistent with the initial phase of cytodifferentiation, followed by rapid proliferation during early decidualization.