This study examined the hypothesis that inhibition of Na,K ATPase with digoxin would enhance the pressor response to aldosterone infusion in conscious sheep. 2. While intravenous infusion of digoxin (10 micrograms/kg per day for 5 days) had no effect on blood pressure and aldosterone infusion (6 micrograms/kg per day for 5 days) increased blood pressure by 7 mmHg, combined infusion of digoxin and aldosterone increased blood pressure by 17 mmHg. 3. The metabolic effects of the combined digoxin and aldosterone infusion were similar to those for aldosterone alone, suggesting that digoxin did not enhance the mineralocorticoid action of aldosterone. 4. The results of this study suggest that changes in Na influx (aldosterone-dependent) and efflux (digoxin-dependent) are important in the genesis of aldosterone-induced hypertension.