In order to achieve a correct diagnosis of drug anaphylaxis using a radioimmunoassay devoid of interferences, we have studied factors leading to false positive or false negative values of plasma histamine. Different steps in sample collection were studied systematically in 30 normal volunteers. False positive values were found in haemolysed samples, with histamine concentrations being correlated with haemoglobin concentrations, and where plasma was aspirated from the white-cell layer. There was no significant increase when a tourniquet or vacuum tubes were used, or when blood tubes were left at 4 degrees C overnight. In 12 patients who experienced an anaphylactic reaction, histamine disappeared from blood 10 times more slowly than expected. False negative values were found in two pregnant women and one heparinized patient. Histamine was remarkably stable in vitro in blood or plasma samples, whereas it disappeared rapidly when plasma from a pregnant woman or a heparinized patient was added to the sample. We conclude that false positive and false negative values are rare when using this radioimmunoassay.