The purpose of this work was to study the involvement of serum hydrophobic IgE in non-specific cross-reactions with hydrophobic drugs such as cyclohexenyl derivatives. Hydrophobic IgE were detected by radioimmunoassay. The results were expressed as the percentage of labelled anti-IgE which were adsorbed to the drug solid phase via IgE of the patient serum. Phenyl-Sepharose IgE-RIA was at 4.6 +/- 0.7%, 125 +/- 6.5% and 17.8 +/- 8.9% in control subjects (n = 24), in atopic patients with positive Phadiatop (n = 30) and in patients with drug allergy (n = 23), respectively. We selected five patients who were allergic to either penicillin, propofol, glafenin or paracetamol and who had a Phenyl-Sepharose IgE-RIA greater than 20%. In these five cases, IgE-RIA were positive (percentage at least twice more than that obtained with control sera) with all the solid phases prepared with hydrophobic drugs such as penicillin, propofol, glafenin, paracetamol and mexiletine. Inhibition of IgE binding by monoethylene-glycol showed that the cross-reactivity was due to hydrophobic binding of IgE to the drug. Three of the five patients were allergic to penicillin and underwent on adverse reaction against another cyclohexenyl derivative, namely propofol and glafenin. In conclusion, we have observed the presence of 'hydrophobic IgE (with positive Phenyl-Sepharose RIA)' in 64% of patients allergic to a hydrophobic drug.