Sprague-Dawley rats were exposed to 450 ppm carbon monoxide (CO) for 6 h per day, 5 days per week for 33 days. The effect of CO on reticulocyte count, hematocrit, hemoglobin concentration, body weight and selected organ weights was measured. Exposure to CO caused a three-fold increase in the youngest reticulocyte population, concomitant with an increase in the total reticulocyte count. Despite continued CO exposure, reticulocyte number and distribution returned to normal by day 9, suggesting that reticulocyte response of the organism to CO had changed. Both hematocrit and hemoglobin concentrations began to increase 16 days after CO exposure and remained at the increased level for the duration of the exposure period. There were no changes in kidney, liver and adrenal weights throughout the course of study. However, spleen weight was increased after 5 days of CO exposure. Left and right ventricular organ weight ratios increased equally at the same time during the study. These results indicate that the increase in the young reticulocyte population and the subsequent increase in total reticulocyte count are the earliest erythropoietic responses to intermittent CO exposure and that CO-induced polycythemia is associated with cardiac hypertrophy in rats.