Abstract The net synthesis of progesterone by human placental homogenates and isolated mitochondria has been described for the first time. The availability of possible blood borne precursors has been screened for in maternal and fetal sera extracts. There appears to be enough pregnenolone in fetal blood to act as one potential source of progesterone formation. Although there is adequate cholesterol present in blood supplying the placenta, this cannot be demonstrated to be a significant source without radioactive tracer studies. This appears to be due to an adequate endogenous precursor, already within the placenta, which is tentatively identified as cholesterol itself. Cholesterol declines as progesterone is formed by the mitochondria. The factor which most affects progesterone formation under these conditions is TPNH. It is hoped to use this isolated steroid synthesizing system to explore some of the possible mechanisms for the endocrine control of pregnancy.