Study of the effect of sex steroids on the development of beta-adrenergic receptors may be essential to an understanding of the mechanisms of both lung maturation and the initiation of labor. (3H)Dihydroalprenolol (DHA) was used to quantify beta-adrenergic receptor sites in mature and immature rabbit lung tissue. DHA binding was rapid, saturable, of high affinity (dissociation constant = 2 nM), and of low capacity (246 to 576 fmoles/mg of protein), and a adrenergic competitors demonstrated both stereoselectivity ([-]isomer much greater than [+]isomer) and a rank order of potency (isoproterenol much greater than norepinephrine greater than epinephrine) characteristic of the beta-adrenergic receptor. beta-Adrenergic receptors in the lung tissue of both mature and immature female New Zealand White rabbits were investigated under various sex steroid situations. Estrogen (diethylstilbestrol, 5 micrograms/day for 10 days) increased the beta-adrenergic receptor site number in immature rabbits compared to matched controls (435 versus 339 fmoles/mg of protein, p less than 0.02 by paired t test). Addition of progesterone (diethylstilbestrol, 5 micrograms/day for 10 days, plus progesterone, 5 mg/day for 3 days) returned the beta-adrenergic receptor site number to control values (321 fmoles/mg of protein, p less than 0.01). In mature rabbits, treatment with progesterone alone (10 mg/day for 4 days) caused a significant reduction in beta-adrenergic receptor site numbers compared to untreated, matched controls (357 versus 493 fmoles/mg of protein, p less than 0.05 by paired t test). in the presence of estrogen, beta-adrenergic receptor activity is enhanced in both mature and immature rabbit lung tissue. Addition of progesterone restores this activity to control values.