After an i.v. application of 100 mg tramadol in 13 healthy volunteers no change in plasma histamine concentration could be detected,( systemic anaphylactoid reactions did not occur, cutaneous reactions were not rated as anaphylactoid since itching and erythema were seen only once after tramadol whereas erythema was also observed twice after saline, blood pressure and heart rate were only very slightly and transiently elevated without any abnormalities in ECG-readings and only side effects typical for opioid therapy were observed.