1 Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a pro-in¯ammatory cytokine secreted by cells of the monocyte/macrophage lineage and has been implicated in the pathogenesis of bronchitis and asthma. 2 In the present study we have evaluated the eect of several cyclic AMP-elevating agents on lipopolysaccharide (LPS)-induced GM-CSF release from human monocytes and the extent to which the anti-in¯ammatory cytokine, interleukin (IL)-10, is involved. 3 LPS evoked a concentration-dependent generation of GM-CSF from human monocytes that was inhibited, at the mRNA and protein level, by 8-Br-cyclic AMP, cholera toxin, prostaglandin E 2 (PGE 2 ) and a number of structurally dissimilar phosphodiesterase (PDE) 4 inhibitors. 4 Pre-treatment of monocytes with a concentration of an anti-IL-10 monoclonal antibody that abolished the inhibitory action of a maximally eective concentration of exogenous human recombinant IL-10, signi®cantly augmented LPS-induced GM-CSF generation. This eect was associated with a parallel upwards displacement of the concentration-response curves that described the inhibition of GM-CSF by PGE 2 , 8-Br-cyclic AMP and the PDE4 inhibitor, rolipram, without signi®cantly changing the potency of any drug. Consequently, the maximum percentage inhibition of GM-CSF release was reduced. Further experiments established that the reduction in the maximum inhibition of GM-CSF release seen in anti-IL-10-treated cells was not due to functional antagonism as rolipram, PGE 2 and 8-Br-cyclic AMP were equi-eective at all concentrations of LPS studied. 5 These data indicate that cyclic AMP-elevating drugs attenuate the elaboration of GM-CSF from LPS-stimulated human monocytes by a mechanism that is not mediated via IL-10. Suppression of GM-CSF from monocytes may explain, at least in part, the ecacy of PDE4 inhibitors in clinical trials of chronic obstructive pulmonary disease.