High blood eosinophil counts in humans are usually due to parasitic infections, allergic processes or malignant diseases. Interleukin-5 (IL-5) is thought to be the principal eosinopoietic stimulus in most of these patients. As the causes of persistent eosinophilia in patients with the idiopathic hypereosinophilic syndrome (HES) are (by definition) unknown, a semi-quantitative assay for IL-5 mRNA in eosinophils and mononuclear cells was carried out using samples from 11 patients with HES. In three patients, unstimulated peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) had markedly raised levels of IL-5 mRNA. In four of five patients studied, phorbol myristate acetate (PMA) stimulation of PBMC induced them to produce more IL-5 mRNA than four healthy subjects. In five patients, bone marrow IL-5 mRNA levels were related to blood eosinophil counts. Blood eosinophils from all six patients tested, and bone marrow granulocytes from four patients had undetectable levels of IL-5 mRNA. It was concluded that HES can be separated into two groups. One has high levels of IL-5 mRNA and/or an enhanced IL-5 mRNA response to stimulation. They may well respond to treatments which inhibit the effects of this cytokine on eosinophil progenitor cells. The second group appears to have a disease which is IL-5 independent.