B-type (brain) natriuretic peptide (BNP) forms a peptide family with A-type (atrial) natriuretic peptide (ANP), which is involved in the regulation of blood pressure and fluid volume. We have demonstrated that BNP is a novel cardiac hormone secreted predominantly from the ventricle and that plasma levels of BNP markedly increase in proportion to the severity of congestive heart failure. Spasm of a major coronary artery (coronary spasm) is the cause of variant angina and can be induced by hyperventilation. We examined whether BNP infusion suppresses coronary spasm in patients with variant angina. The effect of BNP infusion on anginal attacks induced by hyperventilation was studied in 11 patients with variant angina in whom the attacks were reproducibly induced by hyperventilation. This study was performed in the early morning on 3 consecutive days. Fourteen minutes after infusion of BNP was begun (day 2, 0.05 μg/kg/min) or saline (days 1 and 3), hyperventilation was started and continued for 6 minutes. Anginal attacks were induced in all 11 patients by hyperventilation on days 1 and 3, respectively. Anginal attacks were not induced in any patient on day 2 (BNP infusion). Fourteen minutes after BNP infusion was begun, plasma BNP levels increased from 23.7 ± 6.7 pg/ml to peak levels of 2591 ± 255 pg/ml (p < 0.01) and plasma ANP levels increased from 28.9 ± 7.5 pg/ml to peak levels of 69.2 ± 13.2 pg/ml. Five minutes after BNP infusion was finished, plasma levels of cyclic guanosine monophosphate (cGMP) increased from 20.3 ± 7.4 pg/ml to peak levels of 63.5 ± 13.7 pg/ml (P < 0.01). The plasma levels of ANP, BNP, and cGMP did not change after saline infusion and hyperventilation on days 1 and 3, respectively. We conclude that BNP infusion suppresses anginal attacks induced by hyperventilation in patients with variant angina, and that cGMP is related to the mechanism of suppression of the attacks.