These studies have examined the effect of fasting and nutrient loads on sympathetic firing rate in three groups of rats that develop widely divergent degrees of obesity when eating a high-fat diet. Starvation of Sprague-Dawley rats for 24 or 48 h was associated with a decrease in basal sympathetic activity of nearly 25% in the first 24 h and of slightly greater than 30% in 48 h. This decline in sympathetic activity paralleled the loss of body weight and reduction in adipose tissue mass. After starvation for 48 h, Osborne-Mendel rats, which readily develop obesity when eating a high-fat diet, showed a greater decrease in basal sympathetic activity than did the diet-resistant S 5B/P1 rats. A single liquid 36-kcal intragastric meal was associated with an acute 30% increase in sympathetic firing rate in the overnight-fasted Sprague-Dawley rats. The values 3 h after the meal had returned halfway to normal, and by 6 h they were more than 85% of the way to normal. An intravenous injection of glucose produced a greater rise in sympathetic activity in diet-resistant S 5B/P1 rats than in the diet-sensitive Osborne-Mendel rats. These data are consistent with the hypotheses that sympathetic activity is positively related to nutrient status, that it varies between strains of rats, and that it can be acutely increased by an intragastric meal or by intravenous glucose.