When epidermal growth factor was given to rats after partial hepatectomy, hepatic putrescine content was significantly increased at 4, 6 and 10 hr compared with control rats. Ornithine decarboxylase activity was also increased. Hepatic ornithine decarboxylase messenger RNA content was significantly greater than control levels at 2 hr after epidermal growth factor treatment, but not at 10 hr, when the amount of ornithine decarboxylase messenger RNA in control animals was four times that at 2 hr. When actinomycin D was administered 6 hr after partial hepatectomy, hepatic ornithine decarboxylase activity at 10 hr was reduced to half the control levels. This reduction was attenuated by epidermal growth factor treatment at 6 and 8 hr. Hepatic immunoreactive ornithine decarboxylase protein content showed a highly positive correlation with hepatic ornithine decarboxylase activity at 4, 6 and 10 hr, irrespective of epidermal growth factor treatment. Hepatic spermidine N1-acetyltransferase activity was significantly increased at 6 hr compared with control rats. These results suggest that, after partial hepatectomy in rats, exogenous epidermal growth factor may stimulate hepatic putrescine production by increasing ornithine decarboxylase messenger RNA content and altering posttranscriptional ornithine decarboxylase regulation, as well as enhancing spermidine N1-acetyltransferase activity. (HEPATOLOGY 1991;14:901–905).