SUMMARYThe ʻcost of reproductionʼ (i.e. the trade-off between current reproduction and future fecundity and/or survival) is a central concept in life history theory, yet we still know very little about the physiological mechanisms underlying such costs. Recently it has been recognized that reproduction itself or the regulatory (hormonal) mechanisms underlying reproduction might result in ʻcostsʼ (cf. resource-allocation based mechanisms). As one example, it has been suggested that the decrease in hematocrit observed during egg production in birds might be due to antagonistic pleiotropic effects of estrogens. This could generate costs of reproduction by reducing oxygen-carrying capacity during subsequent aerobically demanding stages such as chickprovisioning. Here we show that the reduction in hematocrit during egg-laying is dependent on receptor-mediated actions of endogenous estrogens: blocking estrogen receptors using the anti-estrogen tamoxifen reduces the decrease in hematocrit during egg production in female zebra finches (Taeniopygia guttata) such that hematocrit at the 1-egg stage is not significantly different than pre-breeding, baseline values. We also show that both pre-breeding hematocrit and the decrease in hematocrit associated with egg production are repeatable, and that females with the highest pre-breeding hematocrit values tend to show the largest decreases in hematocrit during egg production. We suggest that hematological changes during egg production are a good candidate mechanism for a regulatory-network based trade-off involving antagonistic pleiotropic effects of estrogens, which otherwise have essential reproductive functions.