The effects of dexmedetomidine (DXM), a novel alpha 2-adrenoceptor agonist, on human performance and mood were studied in a double-blind randomized crossover study in 12 healthy student volunteers. Single IM doses of dexmedetomidine, 0.6 microgram/kg (DXM1) and 1.2 micrograms/kg (DXM2), 80 micrograms/kg midazolam (MID) and saline placebo, were given at one-week intervals. Performance was measured objectively and mood was assessed subjectively with visual analogue scales (VAS) at baseline and 40 min, 2 h, 4 h and 6 h after each injection. Blood pressure and heart rate in the sitting position were measured and venous blood was sampled during each testing round. DXM1 did not significantly impair cognitive (digit symbol substitution), coordinative (tracking) or reactive skills, and at 6 h it shortened reaction time and reduced errors in complex tracking. It produced exophoria, increased body sway with the eyes open and impaired subjective performance on VAS. The higher dose dexmedetomidine also caused impaired cognitive, coordinative and reactive skills (although a trend towards improved coordination was found at 6 h), reduced attention, produced exophoria, increased body sway with the eyes open and caused drowsiness, clumsiness, passiveness and mental slowness on the appropriate VAS scales. MID resembled DXM2 in impaired objective and subjective measures of skilled performance, although the objective effects of MID were of speedier onset and shorter duration. In contrast to MID, DXM caused a significant and dose-dependent decrease in systolic and diastolic blood pressure still detectable 6 h after injection.(ABSTRACT TRUNCATED AT 250 WORDS)