To assess the role of dietary sodium in the regional development and pathogenesis of isoproterenol (ISO)-induced cardiac hypertrophy, male Fischer rats (150-175g n = 65) were divided into control (C) and ISO-treated (I) and three dietary sodium subgroups; low (8.7-13 mEq/kg) (LS), normal (173.9 mEq/kg) (NS) and high (1378 mEq/kg) (HS). Diets began 2 weeks prior to a 7 day continuous infusion of ISO (Alzet miniosmotic pump; 3 mg/kg/day). Mean total heart weight of all I rat groups was larger than in C rats (p less than 0.05). However, low sodium diet ameliorated the percent increase, compared to respective controls, in total heart weight (LSI, 20 +/- 3%; NSI, 26 +/- 6; HSI, 24 +/- 2 (p less than 0.05). Regionally, dietary sodium level did not alter the degree of hypertrophy in the left ventricle plus septum (LVS), but sodium restriction sharply reduced the severe right ventricular (RV) and atrial hypertrophy present in the NSI and HSI rats (LVS: LSI, 18 +/- 2%; NSI, 20 +/- 2; HSI, 15 +/- 2; RV: LSI, 21 +/- 7%; NSI, 45 +/- 9, HSI, 40 +/- 2; atria: LSI, 46 +/- 17; NSI, 73 +/- 23; HSI, 78 +/- 9). Isoproterenol produced diffuse and focal myocardial fibrosis in the subepimyocardium of the LVS with occasional foci of fibrosis in the RV and the subepimyocardium of the LVS. Quantitative analysis demonstrated an increased volume percent of connective tissue limited to the LVS subendomyocardium in all three ISO-treated groups compared to controls (p less than 0.05). These data shows that isoproterenol produces greater hypertrophy of the RV and the atria than the LVS and that dietary sodium restriction selectively decreases the degree of hypertrophy of the RV and the atria produced by ISO. The findings also indicate that the myocardial hypertrophy due to ISO is independent of myocardial injury and is thus, not merely a compensatory response to myocyte loss but rather a direct result of beta-adrenergic stimulation.