Data derived from models of hepatic regeneration indicate that transient, reciprocal changes in polyamines, potent growth promoters, and gamma aminobutyric acid (GABA), an amino acid neurotransmitter with growth inhibitory properties, play important roles in enhancing and inhibiting respectively regulated hepatocyte proliferation. Based on these findings and supportive data derived from studies of human carcinoma tissues and malignant cell lines we propose that permanent increases in polyamine and decreases in GABAergic activity act in concert to contribute to the pathogenesis of hepatocellular carcinoma.