The human hypothalamus produces an endogenous membrane Na(+)-K+ ATPase inhibitor, digoxin, which regulates neuronal transmission. The digoxin status and neurotransmitter patterns were studied in creative and non-creative individuals, as well as in individuals with differing hemispheric dominance, in order to find out the role of cerebral dominance in this respect. The activity of HMG CoA reductase and serum levels of digoxin, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in creative/non-creative individuals, and in individuals with differing hemispheric dominance. In creative individuals there was increased digoxin synthesis, decreased membrane Na(+)-K+ ATPase activity, increased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and decreased tyrosine catabolites (dopamine, noradrenaline, and morphine). The pattern in creative individuals correlated with right hemispheric dominance. In non-creative individuals there was decreased digoxin synthesis, increased membrane Na(+)-K+ ATPase activity, decreased tryptophan catabolites (serotonin, quinolinic acid, and nicotine), and increased tyrosine catabolites (dopamine, noradrenaline, and morphine). This pattern in non-creative individuals correlated with that obtained in left hemispheric chemical dominance. Hemispheric chemical dominance and hypothalamic digoxin could regulate the predisposition to creative tendency.