Peripheral-blood mononuclear cells (MNC) synthesize several histamine-releasing factors (HRF) spontaneously and when stimulated. Some of the characterized cytokines have histamine-releasing activity, especially connective tissue activating peptide III, neutrophil-activating peptide 2 and interleukin-3 (IL-3). At least two species of HRF remain to be characterized. MNC also secrete a histamine release-inhibitory factor (HRIF), which is a highly specific inhibitor, because it antagonizes only HRF. IL-8 resembles the low-molecular-weight species of HRIF in terms of size and specificity.