In our study, we have compared the efficacy and safety of 75-225/day of venlafaxine and 20-60 mg/day of fluoxetine in patients with major depression, diagnosed according to DSM-IV criteria. A total of 61 patients, aged between 27-62 years entered an 8 week, single blind controlled study. Efficacy and safety for both drugs was comparable. The efficacy variables were the Hamilton Depression Rating Scale (HAM-D), Clinical Global Impressions (CGI), and Udvalget for Kliniske Undersegelser side effect rating scales. Response was defined in the protocol as at least a 50 % decrease in HAM-D total score from baseline to endpoint in and an improvement of a least two points in the CGI rating in the therapy phase (week 8). Regarding the comparative efficacy, no significant different between the two treatment groups were found on the HAM-D total score, prospectively defined as the main efficacy measure. Overall safety and tolerability were good for both drugs.