In vitro incorporation of [U-14C]glucose into the myometrium of the rat was measured during the oestrous cycle and early pseudopregnancy. Labelled glucose was metabolized primarily to CO2, extracellular lactate and intracellular acid-soluble material. The specific activity of lactate produced after incubation was higher during oestrus and metoestrus than at other times of the oestrous cycle. During Days 0 to 1 of pseudopregnancy the specific activity of lactate decreased, a reflection of an increased utilization of endogenous substrate. During Days 1 to 4 of pseudopregnancy a gradual rise in glucose uptake occurred. Oestrone, in low (permissive) doses, did not stimulate glucose incorporation above that found in ovariectomized rats, but did block a stimulatory action of progesterone. Similarly, the specific activity of lactate produced during the incubation was increased ten-fold during a 5-day period of progesterone treatment. Oestrogen blocked this action of progesterone, reducing the response to the level observed in intact pseudopregnant rats. The increased dependence upon exogenous glucose for metabolism during early progestation may be a reflection of an action of progesterone on the myometrium which tends to deplete glycogen stores and other endogenous substrates more rapidly than they can be restored by permissive levels of oestrogen.