Although hydralazine is a commonly prescribed antihypertensive agent, reports of acute human poisoning are uncommon. Most of the literature focuses on chronic toxicity, most notably, the drug-induced systemic lupus erythematosus syndrome. A case of acute hydralazine overdose associated with marked ECG ST segment depression in a young adult is presented. Although the patient also had mild hypotension, acidemia, and ethanol intoxication, the ECG abnormality was alarming and suggestive of myocardial ischemia. The patient was managed conservatively in an ICU setting, and the metabolic and ECG abnormalities resolved. No reports of such marked ECG changes associated with acute hydralazine poisoning in a young adult could be found. Clinical and experimental data on acute hydralazine exposure suggest that the possibility of direct drug effects, including positive inotropic and chronotropic effects and myocardial cell injury, should be considered.