The alpha 1-adrenergic receptor mediates the effects of catecholamines on DNA synthesis, as observed in rat liver following a 2/3 partial hepatectomy and in serum-free primary cultures of adult rat hepatocytes exposed to epidermal growth factor. In vitro, norepinephrine action at this receptor heterologously down-regulates epidermal growth factor receptors. In vivo, the alpha 1 receptor's effect on DNA synthesis is restricted to early time points after partial hepatectomy. alpha 1 receptor binding capacity does not vary until 48 hr after liver resection (at which time binding is reduced), but an uncoupling of receptor binding from membrane phosphoinositide turnover occurs between 8 and 16 hr after partial hepatectomy. This change is preceded by a fall in membrane-associated ras p21 detected by radioimmunoassays (46% of control levels by 2 hr after partial hepatectomy). Whether this change represents a loss of p21 protein from membranes or a modification that results in a loss of immunoreactivity is not known.