We evaluated the effect of the opioid antagonist nalmefene on the HPG axis and on food consumption in 14 older impotent men. These patients had low to low normal mean serum testosterone values and normal gonadotrophin levels on screening evaluation. Normal response to GnRH was demonstrated in all the men. The protocol called for 24 hours of evaluation before and during administration of nalmefene 2.0 mg IV every 8 hours for 3 doses. During each 24 hour period, the following determinations were made: serum testosterone, FSH, and LH by five separate determinations between 8 AM and noon; 8 AM and II PM serum cortisols; 24 hour urine collections for free cortisol; and nocturmal penile tumescence (NPT). Food consumption was measured from 4 PM to 10 AM during the two periods. Nalmefene resulted in significant rises in testosterone, LH, and FSH. Nalmefene significantly elevated morning and evening cortisol measurements in all the patients. Nalmefene decreased total calorie consumption, principally by decreasing fat consumption. There was no effect on NPT. We conclude that in older impotent men, nalmefene acutely increases activity of the HPG axis and decreases calorie intake predominantly by decreasing fat consumption.