To compare stress levels between awake craniotomy and craniotomy under general anesthesia, we analysed plasma levels of adrenaline, cortisol, adrenocorticotropic hormone (ACTH), noradrenaline and dopamine in a large series of patients. Patients who underwent awake craniotomy in our hospital (n=110) were evaluated at 5 sample times: immediately after arterial line insertion (T1); immediately after head fixation in a head frame (T2); 1 h after start of incision (T3); immediately after relief of head fixation (T4); and immediately after arrival in the intensive care unit (T5). Levels were then compared with those in 15 patients who underwent craniotomy under general anesthesia. Plasma levels of adrenaline were significantly higher during awake craniotomy than in craniotomy under general anesthesia at T1 to T4. Plasma levels of ACTH, cortisol, and noradrenaline in craniotomy were significantly higher under general anesthesia than those in awake craniotomy at T5.