Exposure to lead has been postulated to contribute to elevated blood p
ressure in humans and has been shown to raise blood pressure in animal
s. The mechanism of action of lead on blood pressure is unknown. We fe
d lead to rats in their drinking water and then examined the productio
n of aldosterone by their adrenal cells in vitro. We also measured exc
retion of aldosterone and corticosterone by intact rats stimulated wit
h corticotropin, with and without lead treatment. At a dose (273 ppm)
that raised blood levels to 30 to 40 mu g/dL, comparable to blood leve
ls in exposed humans, lead induced increased aldosterone secretion in
vitro and in vivo. The effect of lead was most evident when cells or a
nimals were stimulated with aldosterone secretagogues. Experiments in
vitro indicate that exposure to lead in vivo increases activity of one
or more steps in the late pathway of aldosterone biosynthesis. The re
sults suggest that the hypertensive effect of lead involves relative h
yperaldosteronism and may be most evident when secretion of this hormo
ne is stimulated.