Myocardial necrosis was produced in rats by the following regimen: daily injections of dexamethasone and desoxycorticosterone acetate, and gavage with a solution of monobasic sodium phosphate for 5 days, followed by 7 1 2 hours of restraint on the sixth day. Separate groups given the above-described treatment were concomitantly administered 0.14, 0.57, and 2.28 mg. per kilogram per day of nicotine alkaloid in the drinking water. Either phenelzine, 1 mg. per kilogram, or mecamylamine, 12.5 mg. per kilogram, was administered daily to separate groups given the steroid-salt-stress treatment and to other groups also administered 2.28 mg. per kilogram per day of nicotine. Reserpine, 1 μg per animal per day, was injected alternately 3 or 7 days prior to, and also during, steroid-salt-stress treatment, both with and without the administration of 2.28 mg. per kilogram per day of nicotine. The two higher doses of nicotine significantly (P < 0.01) increased the average lesion severity, the per cent mortality, and the per cent incidence of lesions. Myocardial potassium was significantly decreased (P < 0.01 and 0.05). Treatment with mecamylamine or phenelzine did not reduce the response to the steroid-salt-stress treatment, but significantly (P < 0.01) reduced the severity of the response when nicotine was added to the regimen. Seven days of pretreatment with reserpine did not change the response to nicotine, whereas a 3-day pretreatment increased (P < 0.01) the severity of myocardial lesions.