Lungs from near-term fetal guinea pigs (62 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Studies based on 42 preparations investigated effects of epinephrine at different concentrations. Untreated preparations produced lung liquid with no significant change (ANOVA; regression analysis; rates in successive hours 1.37 +/- 0.30; 1.36 +/- 0.30, and 1.28 +/- 0.27 mL.kg-1 body weight.h-1); those given epinephrine at 10(-9), 10(-8), 5 x 10(-8), and 10(-7) M showed significant reductions in production or fluid reabsorption, and there was a linear relationship (r = 0.99) between log concentration and the percent reductions. Above these levels, responses decreased, and at 10(-5) M epinephrine there was no response. There was no evidence for activation of beta-adrenoreceptors; responses to 10(-8) M epinephrine were resistant to propranolol (based on 24 studies), and the specific beta-agonist isoproterenol was without effect (based on 18 studies). However, the alpha-antagonist phentolamine completely eliminated responses to epinephrine at physiological levels (10(-8) M epinephrine; based on 24 studies) and also at levels that gave maximal responses (10(-7) M epinephrine; based on 24 studies). It is concluded that epinephrine is able to promote lung fluid reabsorption at concentrations reported at birth, but that, in contrast with beta-activation in sheep, responses in the guinea pig are mediated through alpha-adrenoreceptors. Clearly, species differences exist.