Alterations in pulmonary uptake of the naturally occurring polyamine spermidine and of an exogenous polyamine substrate analogue, methylglyoxal bis(guanylhydrazone) (MGBG), were investigated during the early phase of compensatory lung growth after partial pneumonectomy (PNX) in rats. In lungs perfused in situ 3 days after left PNX, when a small (14%) but significant (P less than 0.01) increase in right lung mass could be detected, uptake of [14C]spermidine and of [14C]MGBG from the pulmonary circulation was increased. MGBG uptake exhibited saturation kinetics (1-50 microM MGBG), both in lungs of control animals apparent Km, 11.3 microM; Vmax, 479 pmol X g-1 X min-1) and on the 1st and 3rd post-PNX days. In both PNX groups, the apparent Km of the uptake pathway was decreased somewhat (8.5 microM), while Vmax increased progressively to 584 and 678 pmol X g-1 X min-1 at days 1 and 3, respectively. The effects of PNX on MGBG uptake were detected as early as 3 h after lung resection and were no longer evident when compensatory lung growth was completed 14 days after surgery. In rats adrenalectomized 5 days before left PNX, an accelerated onset and increased rate of lung restoration were associated with a doubling of the effect of PNX alone on MGBG uptake.