The association of hypertension and obesity is poorly understood. Studies conducted in our laboratory over the last decade, in conjunction with recent clinical and epidemiological observations, suggest that hypertension in the obese is derived from a fundamental relationship between dietary intake and sympathetic nervous system (SNS) activity. The application of kinetic techniques to the measurement of norepinephrine (NE) turnover rate in sympathetically innervated tissues of laboratory rodents has defined a relationship between the SNS and dietary intake. Fasting or caloric restriction suppresses sympathetic activity in a variety of organs of the rat, including heart and interscapular brown adipose tissue. Overfeeding a mixed, palatable, "cafeteria" diet stimulates sympathetic activity in these same tissues. The stimulatory effect of mixed diets is due to the carbohydrate and fat content, because these two latter nutrients stimulate sympathetic activity even when total caloric intake is not increased. Insulin-mediated glucose metabolism within central neurons associated with the ventromedial hypothalamus (VMH) plays an important role in the relationship between dietary intake and SNS activity as indicated by the following observations: (1) Hypoglycemia (noninsulin-mediated) is associated with suppression of the SNS (despite concomitant adrenal medullary stimulation); (2) 2-deoxyglucose, an intracellular inhibitor of glucose metabolism, decreases sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)