NSAIDs inhibit the conversion of arachidonic acid into Prostaglandin G2 and Prostaglandin H2 which is catalyzed by the enzyme cyclooxygenase (COX). Two genetically distinct isoforms have been discovered, COX-1 and COX-2. While COX-1 is thought to account for homeostatic amounts of eicosanoids, COX-2 is induced during inflammation leading to pathologic amounts of eicosanoids. Since NSAIDs inhibit both COX isoforms, antiinflammatory drug research has refocused to discovering COX-2 inhibitors that do not inhibit COX-1. For this purpose, we have developed a whole cell assay system using the human erythroleukemic cell line HEL as a source for COX-1 and the human monocytic cell line Mono Mac 6 as a source for COX-2. Mono Mac 6 cells express high amounts of COX-2 upon stimulation with lipopolysaccharide (LPS) in the absence of any detectable COX-1 protein. On the other hand, we find HEL cells to naturally express COX-1 protein, but not COX-2. Testing of a panel of NSAIDs as well as some COX-2 specific inhibitors showed that this assay system is suitable for identifying compounds that selectively inhibit either COX-1 or COX-2. This test system offers the advantage of assessing COX-1 and COX-2 inhibitors within the human species, within a similar test set-up, and circumvents the need for tedious purification of either platelets or peripheral blood monocytes.