1. The effect of omega-3 fatty acid supplementation on alpha 1-adrenergic receptor-mediated phosphoinositide turnover in the hearts of 6-week streptozotocin diabetic rats was studied. 2. The diabetic state was characterized by decreased body weight gain, hypoinsulinemia and hyperglycemia. Omega-3 fatty acid treatment did not have any significant effects on the above parameters. 3. Plasma triglyceride and cholesterol levels were significantly higher in diabetic rats compared with controls. 4. Omega-3 fatty acid treatment reduced the plasma triglyceride levels in the diabetic rats, whereas plasma cholesterol levels remained unaffected. 5. Norepinephrine (10 and 100 microM) stimulated inositol monophosphate (IP1) formation was significantly decreased in the diabetic rat heart compared with controls. Omega-3 fatty acid treatment had no significant effect on the norepinephrine-mediated IP1 formation in these rats. 6. Inositol bisphosphate (IP2) formation in response to 100 microM of norepinephrine was significantly lower in the diabetic rat heart; which was also not affected by omega-3 fatty acid treatment.