Left ventricular (LV) diastolic filling is limited by the constraining effects exerted by the pericardium (PE) and the lung/chest wall. The aim of the present study was to assess the validity of various estimates of external cardiac constraint, compared to pericardial surface pressure (Ppe) measured lateral to the LV myocardium. In nine anesthetized dogs we measured Ppe, pleural surface pressure (Ppt) (lateral to the pericardium) and esophageal pressure (Pes) under conditions of volume loading and positive end-expiratory pressure (PEEP). We measured Ppe and Ppl with flat, liquid-containing silastic rubber balloons and Pes with an air-containing cylindrical balloon. After instrumentation, the chest was resealed and continuous suction (-5 mm Hg, 1 mm Hg = 0.133 kPa) was maintained. Volume loading with incremental intravenous infusions of saline was used to increase LV end-diastolic pressure to 20-25 mm Hg. PEEP of 0, 10 and 20 mm Hg were applied at baseline and after each increment of volume loading. At low volume, increases in PEEP caused simultaneous increases in LV end-diastolic pressure (P less than 0.01) and in Ppe (P less than 0.0001) but a reduction in transmural LV pressure (P less than 0.0005). Ppl and Pes both increased with PEEP (P less than 0.001 and P less than 0.01, respectively). However, Ppe always exceeded Ppl, while Pes remained at only approximately 1/3 Ppl throughout. Volume loading caused a significant increase in Ppe (P less than 0.0001) and a smaller, but significant increase in Ppl (P less than 0.05). Pes remained unchanged during volume loading. Thus external cardiac constraint increased markedly during volume loading and PEEP as evidenced by a marked elevation of Ppe. Both Ppl and Pes markedly underestimated this increase. Therefore, calculation of transmural LV pressure by subtracting pleural or esophageal pressure from intracavitary pressure can lead to overestimation of LV preload. The decrease in cardiac output during PEEP occurs secondary to decreased preload, i.e. decreased transmural pressure and end-diastolic dimension. Analysis of performance using cardiac function curves does not suggest a change in contractility with PEEP.