The salient sign of acutely lethal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication in rats is hypophagia along with a prominent body weight loss. Endogenous opioid peptides have been implicated as modulators of food intake. In the present study, female rats of both the most TCDD-susceptible (Long-Evans [L-E]; LD50 9.8 micrograms/kg) and the most TCDD-resistant strain (Han/Wistar [H/W]; LD50 > 7200 micrograms/kg) were exposed to a single dose of 50 micrograms/kg TCDD ip. This treatment is usually lethal within 1-6 weeks to all L-E rats and nonlethal to all H/W rats. The animals were killed at 1, 4 or 10 days after the treatment. beta-Endorphin-like immunoreactivity (beta-END-LI) was determined by a validated RIA method in the hypothalamus, pituitary, pancreas, duodenum and plasma. TCDD decreased plasma beta-END-LI concentration by 24-37% at every time point of measurement in L-E rats alone. By contrast, feed-restricted controls exhibited an increase of similar magnitude on day 4. Pancreatic beta-END-LI was also elevated in feed-restricted controls at that time point as compared with either the ad libitum control or TCDD group. TCDD appeared to shrink the pituitary gland in both strains by day 4. Pituitary weight was similarly lowered in TCDD-treated rats and feed-restricted controls at the last time point and this reduction was reflected in pituitary beta-END-LI content. Thus, TCDD affects selectively plasma beta-END-LI levels and this impact correlates with its lethality in these strains.