The sensitivities of PDE-4 enzymes from smooth muscle and inflammatory cell sources from different species to a range of structurally diverse compounds were compared. All inflammatory cell PDE-4 sources displayed good crosscorrelations in their sensitivity to inhibition by these compounds. Similarly, PDE-4 enzymes from smooth muscle sources were well-correlated; however, there was no crosscorrelation between PDE-4 from smooth muscle sources and those of inflammatory cell sources, possibly reflecting differences in subcellular location of enzymes as well as subtype expression. The present study concludes that PDE-4 preparations from smooth muscle sources as well as those from inflammatory cell sources may be used to model the potential smooth muscle cell relaxing properties and anti-inflammatory properties of a compound in relation to human asthma.