Male rats received doxorubicin (DXR) 2 mg/kg or phosphate buffered saline (PBS) weekly by the SC route for 13 weeks and were sacrificed at 14 and 19 weeks, one and six weeks, after the last dose, respectively. Heart phospholipase A2 activity in the 1000 X g supernatant was unchanged between DXR and PBS-treatment groups at both 14 and 19 weeks. In vitro heart microsomal syntheses of PGD2, PGE2, PGF2 alpha, and 6-keto-PGF1 alpha were significantly elevated in DXR-treated rats over controls at 14 weeks. In contrast, syntheses of TxB2, PGE2, and PGF2 alpha in DXR-treated rats were significantly depressed from controls at 19 weeks. In vitro heart metabolism of PGF2 alpha in the 100,000 X g supernatant fraction was significantly elevated in DXR treated rats over controls at 14 weeks, but unchanged from controls at 19 weeks. It was concluded from the findings of the present study that increased prostaglandin synthesis may play a role in the mediation of cardiac injury induced by doxorubicin.