We have compared the pathways of arachidonic acid (C 20:4) metabolism in platelets from ten patients with Philadelphia chromosome-positive CML with those of seven normal subjects. Platelets were incubated with 3H-arachidonic acid, gel-filtered, and treated with thrombin (5 U/ml). The cyclooxygenase and lipoxygenase-derived products and free arachidonic acid released from the platelets were separated by high pressure liquid chromatography and their radioactivity determined. The total uptake of 3H-C 20:4 by platelets from CML patients did not differ from controls, but the release of radioactivity in response to thrombin was significantly lower (p < 0.01) in CML patients (32.3% +/- 4.9% of total radioactivity was released from control platelets; 19.0% +/- 7.4% from CML platelets). Both cyclooxygenase and lipoxygenase-derived products were reduced, but there was no specific pattern of abnormality. Although there was no direct correlation between either the WBC or platelet count and impairment of platelet C 20:4 metabolism, the platelets from three patients with accelerated disease released the lowest total amount of 3H-C 20:4 metabolites. In a single patient, studied before and after successful chemotherapy (hydroxyurea), severe abnormalities in platelet arachidonic acid metabolism returned to normal after treatment.