The peripheral arterial chemoreceptor response to hypoxemia in the fetus is predominantly cardiovascular, invoking a fall in heart rate and a variable change in blood pressure. No quantifiable measure of chemoreceptor activity has yet been described in the intact fetus. We described the course, quantified the overall response, and defined the reproducibility of the heart rate response to acute hypoxemia in 22 late-term unanesthetized fetal sheep. Fetuses were chronically instrumented and studied between 1-6 days postoperatively. Acute hypoxemia was induced by occluding a balloon cuff around the common hypogastric artery. We performed 151 occlusions, starting at an initial saturation of 66 +/- 11%, decreasing saturation by 8-50%. Soon after balloon inflation, arterial oxygen saturation fell, followed by a decrease in heart rate. We calculated delta HR/delta sat, the fall in heart rate divided by the fall in saturation. Multiple linear regression analysis showed a sensitive chemoreflex, delta HR/delta sat averaging 2.5 +/- 1.2 bpm.%saturation-1. Initial saturation did not alter the first phase of the response (from the onset of the decrease in oxygen saturation to the onset of the decrease in oxygen saturation to the onset of the decrease in heart rate), but it did increase the overall response (delta HR/delta sat) when saturation was less than 65%. After adjusting in the lower range of initial saturations to that predicted at 65%, delta HR/delta sat was very reproducible within animals, with intra-animal variance being only 7% of inter-animal variance.(ABSTRACT TRUNCATED AT 250 WORDS)