1. The effects of nafazatrom, nordihydroguaiaretic acid (NDGA) and quercetin on Ca2(+)-induced vasoconstriction were studied in isolated rabbit ear arteries. 2. The arteries were perfused with Ca2(+)-free and high K+ (75 mM) Krebs bicarbonate buffer. Constriction of the artery was induced by addition of Ca2+ (1.5 mM) to the perfusion fluid. 3. Indomethacin (1 microM) did not alter the response to Ca2+. 4. Nafazatrom (2 or 5 microM) produced a concentration-dependent inhibition of the constrictor response to Ca2+ ranging from 4 to 23% after 1 hr of perfusion and 26 to 62% after 3 hr. 5. Similar effects were obtained with NDGA and quercetin (0.5 and 1 microM). 6. The inhibitory effects of nafazatrom and quercetin were antagonized by Ca2+ (2.5 mM) or Bay K 8644 (1 microM), a calcium channel activator. 7. Ca2(+)-induced contractions recovered within 30 min after discontinuation of perfusion with quercetin, whereas nafazatrom and NDGA had longer durations of action. 8. These results suggest that inhibitors of lipoxygenase antagonized Ca2(+)-induced vasoconstriction and that products of lipoxygenase metabolism may facilitate Ca2+ entry into vascular smooth muscle cells.