Background: Both glucocorticosteroids and phosphodiesterase (PDE) type 4 inhibitors have modulatory effects on PBMC cytokine secretion. In this study we compared the effect of glucocorticoids and PDE inhibitors on IL-10 and TNF-⍺ production by PBMCs from nonatopic versus atopic individuals. Methods: PBMCs were incubated with glucocorticoids (beclomethasone dipropionate and mometasone furoate) or media alone for 24 hours. PDE type 4 inhibitors (Ro20-1724 and rolipram) were then added to the cells preincubated with media. After stimulation with PHA, incubation was continued for 48 hours. The cytokine content of the cell supernatants was determined by ELISA. Results: PDE-4 inhibitors and glucocorticoids caused a concentration-dependent inhibition of the secretion of both TNF-⍺ and IL-10. PDE-4 inhibitors were over 20 times more potent in suppressing cytokine secretion by PBMCs from atopic than nonatopic donors, and approximately 5 times more potent in preventing TNF-⍺ than IL-10 secretion. In cells from nonatopic donors, glucocorticoids inhibited the production of TNF-⍺ to a greater extent than IL-10, but these drugs were more potent in cells from nonatopic than atopic persons. Conclusion: In conclusion, both PDE-4 inhibitors and glucocorticoids suppress secretion of TNF-⍺ and IL-10. However, because PDE-4 inhibitors are more potent in suppressing cytokine secretion by PBMCs from atopic individuals but less potent in inhibiting production of IL-10, PDE-4 inhibitors may have greater therapeutic potential than glucocorticoids in allergic diseases. (J Allergy Clin Immunol 1998;102:797-804.)