Fig. 4. Melatonin and cortisol plasma concentrations. The plasma melatonin ( A ) and cortisol ( B ) concentrations (mean ± SD) measured at midnight, 3:00 am, and 6:00 am are presented. A demonstrates the normal nocturnal increase and decrease of melatonin in both the saline–placebo (Saline) and remifentanil–placebo (Remi) groups. In the saline–melatonin (Mel) and remifentanil–melatonin (Remi/mel) groups, the plasma concentrations of melatonin were measured only to confirm the presence of supranormal concentrations. B demonstrates the suppression of plasma cortisol concentrations by remifentanil, which became statistically significant at the 6:00 am time point. Melatonin did not have a statistically significant effect on the cortisol concentration at any single time point, but the area under the curve demonstrated suppression of cortisol concentrations by melatonin ( P = 0.045).