To identify the effects of acute starvation on endogenous opioids in man, plasma β-endorphin (β-EP) was measured in 17 patients before, during and after fasting. Patients were assigned a posteriori into two groups: group A, comprised of 11 patients able to tolerate 5-7 days of fasting, and group B, comprised of 6 patients able to tolerate 10 days of fasting. Changes in plasma β-EP, serum cortisol, circulating nutritional markers, and their relative levels were assessed on the 5th and 10th days of fasting, and on the 5th and 10th days of the refeeding period. Beta-EP had increased by the 5th day (group A: 4.74 ± 0.42 to 6.91 ± 0.65 pmol/l, p < 0.01; group B: 3.60 ± 0.48 to 5.14 ± 0.22 pmol/l, p < 0.05, and remained at 5.05 ± 0.65 pmol/l on the 10th day (group B: 0.05 < p < 0.1) during fasting. Group B had lower levels of plasma β-EP on the 5th day of fasting than group A (p < 0.05). However, serum cortisol levels changed similarly in both groups. Plasma β-EP showed no significant correlation with either the percentage of body weight lost or the body mass index (kg/m<sup>2</sup>) over this study period. These findings indicate that plasma β-EP is elevated in the early phase of fasting, while not directly being associated with body weight changes. Plasma β-EP is lower and less activated in subjects who are able to tolerate fasting for longer periods.