Lungs from near-term fetal guinea pigs (60 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye-dilution method. Studies of 30 fetuses showed that untreated preparations produced fluid at 1.34 +/- 0.21 ml.h-1.kg body wt-1, but epinephrine at concentrations known at delivery (10(-8) and 10(-7) M) produced significant reductions or fluid reabsorption (analysis of variance, regression analysis); at high levels (10(-6) and 10(-5) M, epinephrine had no effect. Maximal responses from 10(-7) M epinephrine involved alpha-adrenoreceptors, since they were abolished by 10(-6) M phentolamine (alpha-antagonist) but were unaffected by 10(-6) M propranolol (beta-antagonist; n = 36). Activation was through alpha2-adrenoreceptors, since responses were abolished by 10(-4) M yohimbine (alpha-antagonist; n = 24) but were resistant to 10(-5) M prazosin (alpha 1-antagonist; n = 24). At high levels of epinephrine (10(-5) M), where responses did not normally occur, reductions in lung liquid production were large if prazosin was also present (n = 24), and increases were significant if yohimbine was included (n = 24). In guinea pigs, epinephrine appears to activate lung fluid reabsorption through alpha 2-adrenoreceptors; at high concentrations only, it can also increase production through alpha 1-adrenoreceptors. Therefore, species differences appear to exist.