We studied the ability of monocytes to metabolize [3H]arachidonic acid (AA) provided exogenously by activated T cells, and the extent to which dexamethasone suppressed eicosanoid production by normal and atopic cells.[3H]AA metabolites were identified using a reverse-phase high pressure liquid chromatography system (HPLC). Unstimulated and PHA-stimulated T cells from normal and atopic subjects exhibited a similar uptake and time-dependent release of radiolabel, 90% of which was identified as free AA. The addition of autologous normal and atopic monocytes to these cultures enhanced the release of radiolabel, even in the absence of stimulation with mitogen. Atopic T cell/monocyte cultures released significantly (P= 0.046) more radiolabel than normal cells when stimulated with PHA. Furthermore, the monocytes from both normal and atopic subjects metabolized T cell derived [3H]AA into cyclo-oxygenase (CO) and lipoxygenase (LO) products. Under unstimulated conditions, atopic cells produced significantly (P= 0.04) less CO products than normal cells. In contrast, under PHA and calcium ionophore-stimulated conditions, the atopic cells produced significantly (P= 0.048) more prostaglandins than normal donor cells. Furthermore, although the total release of radioactivity was comparable in both groups, significantly less (P= 0.02) free AA remained in ionophore-stimulated culture supernatants from atopic cells. In order to study the regulation of AA release by normal and atopic T cells, dexamethasone (1 μm) was added to T cell cultures. Dexamethasone inhibited the release of [3H]AA from normal T cells to a significantly (P= 0.003) greater extent than it did to atopic cells. Our studies suggest that mononuclear cells from atopic subjects have abnormalities both in AA metabolism and the regulation of its release, supporting the hypothesis that allergic individuals exhibit disordered cellular immunoregulation and enhanced inflammatory responses.