Monocytes are being characterized for the expression levels of CD40, CD80, CD86, CD120b, and the gamma interferon receptor alpha chain. These studies have identified two patients with gamma interferon receptor alpha chain deficiency, and the molecu-lar level of this defect is being actively examined. In addition, one patient with interferon gamma receptor beta chain deficiency also has been characterized at the molecular level. As a consequence of these studies, an intracellular flow cytometric method for evaluating STAT protein phosphorylation has been developed and validated. This approach is being investigated for a wide variety of activation associated protein alterations and appears to be useful in screening for patients with severe combined immunodeficiency due to defects in the common gamma chain and JAK3.