The relationship between bath PO2 [partial O2 pressure], intramural prostaglandin [PG] synthesis and vessel tone in isolated coronary arteries of cattle was studied. The basal output of PG under 95% O2-5% CO2 (580 mmHg) was elevated markedly when the PO2 was decreased to 47 mmHg, but extreme hypoxia (9 mmHg) sharply curtailed output. The coronary vessels responded to 47 mmHg with relaxation but they contracted when the PO2 was decreased further to 9 mmHg. Known inhibitors of PG synthesis attenuated both the hypoxia-induced relaxations and contractions. Analysis of the effects of extreme hypoxia and of inhibitors of PG synthesis on tone indicated that both suppress PG production. Coronary PG synthesis is accelerated by hypoxia unless the O2 deprivation is so severe as to limit the availability of O2 for synthesis.