1. 1. Pentoxifylline [3,7-dimethyl-l-(5- oxo-hexyl)-xanthine] inhibits the soluble 3' 5'-cyclic AMP phosphodiesterase (PDE I) and the particulate 3',5'-cyclic AMP phosphodiesterase (PDE II) isolated from bovine and human platelets. 2. 2. The inhibition of PDE I and PDE II by pentoxifylline is of an uncompetitive type. 3. 3. In in vitro experiments, incubation of bovine platelets (30 min at 37°C) with pentoxifylline (5 × 10 −4M) increases the cAMP concentration by 25.6%. 4. 4. During incubation (30 min at 37°C) of bovine platelets with 14C-labeled pentoxifylline (5 × 10 −4M) virtually none of the pentoxifylline was incorporated into the platelets. 5. 5. During isolation of the bovine platelet membrane, a cyclic AMP phosphodiesterase (PDE) apparently attached to the membrane is observed. 6. 6. The phosphorylation of the platelet membrane with γ- 32P-ATP is catalysed by 3′5′-cyclic AMP. 7. 7. The interpretation of these experimental data is compatible with the hypothesis that pentoxifylline inhibits platelet aggregation by inhibition of membrane bound PDE and raising cyclic AMP in the same pool. The 3′5′-cyclic AMP activated protein kinase catalyses phosphorylation of the membrane protein by ATP. This results in an increase in the negative charge of the membrane and consequently in the inhibition of platelet aggregation.