The effects of prostaglandin E2 (PGE2) and iloprost on the cardiac response to adrenergic nerve stimulation in guinea-pig atrial and ventricular preparations have been studied. 2. In guinea-pig isolated atria both PGE2 (0.1-10 nM) and iloprost (0.1-3 microM) concentration-dependently reduced the cardiac response to adrenergic nerve stimulation. 3. The inhibition of cyclo-oxygenase by indomethacin and acetylsalicylic acid potentiated the response to nerve stimulation in the atrial preparations. 4. Arachidonic acid (1-10 microM) reduced the response to nerve stimulation in atria. This effect was prevented by indomethacin and acetylsalicylic acid. 5. In guinea-pig ventricles PGE2 and iloprost were found to be effective at higher concentrations than in atrial preparations: arachidonic acid, indomethacin or acetylsalicylic acid did not modify the cardiac response to adrenergic nerve stimulation. 6. These results suggest a different modulator role for endogenous prostaglandins in atrial and ventricular tissue.