We selectively reviewed potassium (K) metabolism during human gestation, focusing on the influence of progesterone on renal K excretion. Approximately 300 mEq of K is gained during pregnancy. Two-thirds of it are in the products of conception, but little is known about renal K handling during gestation. We have suggested that progesterone may play a role in preventing the kaliuresis that normally occurs when aldosterone levels are elevated and substantial quantities of sodium are presented to distal nephron sites. In addition, we hypothesize that subtle K secretory problems, such as those known to occur in sickle cell disease, may be aggravated during gestation, probably due to elevated circulating levels of progesterone.