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To evaluate the relationship between thallium-201 lung activity and pulmonary fluid volumes, we compared thallium pulmonary scintigrams with measures of intravascular (PBV), extravascular (EVLW) and total lung water (TLW) during gradual left atrial (LA) hypertension and then serially after the acute release of pressure. The study group was composed of nine mongrel dogs who were each studied at seven levels of elevated LA pressure, and then every 15 minutes for 2 hours after the acute release of pressure. During LA pressure (congestion phase) elevation, lung counts (normalized for myocardial activity), correlated best with TLW (r=.91), rather than PBV (r=.84) or EVLW (r=.81). After the release of pressure (recovery phase), lung counts correlated well with EVLW (r=.92) and TLW (r=.82), but not with PBV (r=.28). Postmortem lung counts from 197 separate lung sections correlated well with the corresponding wet weight/dry weight ratio from that section (r= .81). Thus, we conclude that changes in pulmonary thallium emissions during cardiogenic pulmonary edema relate to corresponding changes in pulmonary fluid volumes. During congestion, the confounding effects of nonlinear increases in EVLW and PBV make thallium emissions more a marker of TLW than either the intravascular or extravascular pulmonary fluid compartment. After pressure release, PBV immediately returns to normal, at which time EVLW and pulmonary emissions correlate closely. These latter data, more applicable to postexercise stress thallium data, lend support to the hypothesis that elevated pulmonary emissions during postexercise thallium scintigrams reflect elevations in EVLW that develop during exercise.