In a multicenter study 153 in- and outpatients suffering from severe pain were treated for three weeks with capsules containing 50 mg 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol, Tramal). The daily dosage was limited to 400 mg. At the end of the third week the patients received in a randomized double-blind manner 1.6 mg naloxone or saline (both i.m.) to evaluate the risk of developing dependence during the 3-week tramadol treatment (precipitation test). A total of 109 patients completed the trial. Development of tolerance was not observed as was evident from a constant daily tramadol dose associated with constant analgesia. The median net withdrawal scores for the naloxone treated group (mean = 0, Xmin = 0, Xmax = 13) and for the saline treated group (mean = 0, Xmin = 0, Xmax = 5) indicate absence of dependence. The outcome of the study thus suggests that tramadol under the conditions described does not induce dependence.