This study investigated diurnal variations in the affective and endocrine response to opioid blockade in man and whether there were effects related either to the dose of naloxone or the time of day at which it was given. Normal male subjects were given an intravenous bolus of either 0.2 mg/kg (study 1) or 1 mg/kg naloxone (study 2) or control infusions at two time points (0900 or 1800 hours) in a single-blind crossover design. Before and following each infusion, mood was measured by the Profile of Mood States (POMS) and a visual analogue scale (VAS), and blood samples taken at 15-min intervals. Cortisol, LH ACTH and vasopressin (study 2 only) were measured. Blood pressure and heart rate were also monitored. The lower dose of naloxone had no effect on overall mood (POMS), though tension and confusion were increased in the afternoon. The VAS showed increased depression in the afternoon, and heightened tension, sleepiness and reduced ability to concentrate at both times of day. The higher dose increased overall dysphoria at both time points, though the tension and depression subscales were not altered. VAS depression and tension were increased, and there were changes in sleepiness. Subjective reports showed that 45% of the subjects correctly identified the drug treatment at the lower dose compared with 89% at the higher one. ACTH increased after both doses of naloxone irrespective of time of day. Cortisol was also raised by naloxone; the effect was greater in the afternoon for the lower dose, but not the higher.(ABSTRACT TRUNCATED AT 250 WORDS)