Circulating biogenic amines, such as serotonin or norepinephrine, are cleared by the lung and can be considered as indicators of pulmonary endothelial integrity. An iodinated norepinephrine analogue, metaiodobenzylguanidine (MIBG), is extracted in the lung by an active, saturable transport system. In order to investigate the use of MIBG lung extraction to detect minimal lung endothelial cell lesions, an experimental model of initial pulmonary vascular lesions was developed in rats using repeated daily intraperitoneal injection of bleomycin (BLM: 2 U/100 g body weight) over a 5-day period. At this time, a significant decrease of serum angiotensin-converting enzyme activity, an index of endothelial cell metabolism, was observed (214 +/- 11 U/ml in controls as compared with 182 +/- 11 U/ml in BLM-treated rats, P less than 0.05); electron microscopy showed the presence of typical but minimal endothelial cell lesions (blebbing). MIBG extraction (%EMIBG) was measured using the isolated perfused lung model after a 10-min steady-state period and 2 min of perfusion with 123I-MIBG (0.1 microCi/ml) and 125I-labelled human serum albumin (HSA) (0.2 microCi/ml). Intraperitoneal administration of BLM to rats for 5 days resulted in a significant decrease in pulmonary extraction of MIBG. %EMIBG declined from a control value of 24.7% +/- 1.1% in controls to 19.3 +/- 1.6% in BLM-treated rats (n = 27, P less than 0.05; -21.2%). HSA lung extraction, used as an estimate of nonspecific residual lung activity, was not different in the lungs of BLM-treated rats as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)