Using a recently established porcine model, it was clearly shown that oral histamine administration is extremely dangerous in the presence of diamine oxidase (DAO) blockade. Due to the severity of the symptoms (20% death) and the clinical relevance, further interest has been focussed on strategies to prevent or alleviate food induced histaminosis. In a randomized controlled trial, 10 pigs under DAO blockade were challenged with oral histamine (60 mg). Half of these animals received a prophylactic premedication with a combination of H1- and H2-receptor antagonists. As expected, all animals developed a massive increase in plasma histamine levels, with significantly higher values in the control group (median: 123 ng/ml) compared to the antihistamine group (median: 32 ng/ml). In contrast, clinical symptoms were only observed in the control group. The maximum fall in mean arterial pressure (hypotension) was 60 mmHg (median for control group) but only 15 mmHg (median) under antihistamine pretreatment. These results firstly provide further evidence for the causal role of histamine in the new disease concept and secondly enable us to investigate appropriate therapeutic measures for patients at risk.