Summary Suppression of erythropoietin secretion in lactating and normal female mice by 60% oxygen decreased their RCV and reticulocyte output and abolished plasma erythropoietic activity. In normal mice and in nonlactating postpartum mice, administration of prolactin resulted in an increase of RCV and of PV to values equivalent to those of 15-day postpartum lactating mice. Administration of prolactin to lactating mice and to normal female mice concurrently exposed to hyperoxia prevented the decrease of RCV and of PV which resulted from exposure to hyperoxia alone. The data indicate that in mice, the prolactin preparation used acted as an erythropoietic stimulant and caused a plasma hypervolemia which was not related to the action of erythropoietin.