OBJECTIVE To determine the variability in the size and distribution of the first septal perforating artery (FSPA). MATERIAL AND METHODS In this pilot study, 10 fresh autopsy hearts from patients who did not have hypertrophic cardiomyopathy (HCM) or clinical evidence of coronary artery disease were evaluated for the variability in the size of the FSPA. The size of the FSPA was also measured during coronary angiography in 8 patients with HCM who were undergoing alcohol septal ablation. RESULTS Of the 10 autopsy hearts, 2 had a large FSPA (> or = 1.0 mm in maximal diameter) with prominent septal myocardial distribution, 2 had a medium-sized FSPA (0.5-0.9 mm), 2 had a small FSPA (0.1-0.4 mm), 3 had a tiny FSPA (< 0.1 mm), and 1 had an indiscernible ostium. In 2 patients the FSPA supplied the right ventricular free wall. In 4 patients the basal ventricular septum was incompletely supplied by the FSPA. Of the 8 patients with HCM, the FSPA was larger than 2 mm in diameter in 2 patients, 1 to 2 mm in 4, and smaller than 1 mm in 2. The distance between the left anterior descending coronary artery ostium and the origin of the FSPA ranged between 13.1 and 37.4 mm, indicating a large variation in the size and distribution of the FSPA. CONCLUSIONS Variability in the size and distribution of the FSPA in patients without HCM was substantial. Areas of the heart other than the basal septum were supplied in some patients by the FSPA. In other patients the FSPA did not supply the entire basal septum. Similar findings were noted in patients with HCM. A detailed evaluation of the distribution of the FSPA may be necessary in all patients with HCM who are undergoing alcohol septal ablation.