A family with coexistent hypotension, recurrent respiratory infection owing to immune deficiency, motor tics, obsessive-compulsive disorder, major depressive disorder, early onset osteoporosis, low body mass index, bulimia nervosa, and healthy aging is described. The family members had the following behavioral patterns: hyposexual, nonspiritual, noncreative, somnolent tendency, increased bonding and affectionate behavior and nonaddictive tendency. All members in the family were right-handed left hemispheric dominant. The human hypothalamus synthesizes an endogenous membrane Na+K+ ATPase inhibitor: digoxin. This has been extensively documented in the literature.1,2,3,4,5 Structurally, digoxin is a steroidal glycoside and is synthesized in the human hypothalamus by the isoprenoid pathway.3,4,5 From our laboratory, 14C labeled acetate studies have demonstrated that endogenous digoxin is synthesized by the isoprenoid pathway. Alteration in the endogenous membrane Na+K+ ATPase inhibitor, digoxin has been documented in depression, essential hypertension, and syndrome X.1,2 Digoxin can function as a modulator of synaptic transmission in multiple neurotransmitter systems.4 Digoxin and alterations in membrane Na+K+ ATPase activity can modify intracellular calcium/magnesium ratios and may also function as a immunomodulator.3 Therefore, it was hypothesized that endogenous digoxin would play a role in the pathogenesis of the disorders described in the indexed family (e.g, hypotension, major depressive disorder, osteoporosis, recurrent respiratory infection, low body mass index). Other isoprenoidal metabolites of significance are ubiquinone (regulate mitochondrial function), cholesterol (component of cellular membranes), and dolichol (regulate N-glycosylation of proteins). The isoprenoidal pathway, glycoconjugate metabolism, neurotransmitter patterns, free radical metabolism, and membrane composition were studied in the indexed family. Glycoconjugates, sialoligands and fucoligands are involved in immunomodulation and function as acute phase reactants in infections. Free radicals mediate the phagocytic killing of bacteria and viruses. They could, therefore, be of significance in the pathogenesis of recurrent respiratory infection. Digoxin can modulate the neutral amino acid-tryptophan/tyrosine transport, and hence regulate their cellular metabolism. Tryptophan and tyrosine catabolic patterns were studied in order to delineate the neurotransmitter patterns involved in the psychiatric/psychological disorders in the family, as clinical treatment of these disorders is dependent on modulation of neurotransmitter function. Alterations in neuronal membrane structure/function have been described in depressive illness and drugs such as lithium, which is used to treat bipolar mood disorder and can alter membrane function. The isoprenoid pathway metabolites, ubiquinone and dolichol, can regulate membrane composition and structure. Red blood cell membrane composition was studied as a marker for such parameters. Since digoxin and changes in membrane Na+K+ ATPase activity was the only common possible etiopathogenetic factor underlining hypotension, major depressive disorder, osteoporosis and recurrent infection, alteration in the digoxin status, and the isoprenoid pathway cascade were hypothesized as the primary dysfunctions in the family. Thus, the data on digoxin status and isoprenoid pathway related cascade, as well as possible modulation of both biochemical parameters, are of clinical significance in the treatment of the disorders noted in the indexed family. Since digoxin can regulate synaptic transmission in multiple neurotransmitter systems and, possibly, hemispheric dominance, the isoprenoid pathway was also compared in right hemispheric and left hemispheric dominance in order to find whether hemispheric dominance plays a role in the genesis of the disorder.