Effects of regional diastolic pressure differences within the left ventricle on the measured transmitral pressure-flow relation were determined by simultaneous micromanometric left atrial (LAP) and left ventricular pressure (LVP) measurements, and Doppler echocardiograms in 11 anesthetized, closed-chest dogs. Intraventricular pressure recordings at sites that were 2, 4, and 6 cm from the apex were obtained. Profound differences between these sites were noted in the transmitral pressure relation during early (preatrial) diastolic filling. In measurements from apex to base, minimum LVP increased (1.6 +/- 0.7 to 3.1 +/- 0.8 mm Hg, mean +/- SD); the time interval between the first crossover of transmitral pressures and minimum LVP increased (31 +/- 3 to 50 +/- 17 msec); the slope of the rapid-filling LVP wave decreased (74 +/- 13 to 26 +/- 5 mm Hg/sec); the maximum forward (i.e., LAP greater than LVP) transmitral pressure gradient decreased (3.6 +/- 1.3 to 2.1 +/- 0.7 mm Hg); the time interval between the first and second points of transmitral pressure crossover increased (71 +/- 9 to 96 +/- 13 msec); and the area of reversed (i.e., LVP greater than LAP) gradient between the second and third points of transmitral pressure crossover decreased (101 +/- 41 to 40 +/- 33 mm Hg.msec). During atrial contraction, significant regional ventricular apex-to-base gradients were also noted. The slope of the LV A wave decreased (26 +/- 10 to 16 +/- 4 mm Hg/sec); LV end-diastolic pressure decreased (8.1 +/- 2.0 to 7.4 +/- 2.0 mm Hg), and the upstroke of the LV A wave near the base was recorded earlier than near the apex. All differences were significant at the 0.05 level. Simultaneous transmitral Doppler velocity profiles and transmitral pressures were measured at the 4-cm intraventricular site. The average interval between the first and second points of pressure crossover and between the onset of early rapid filling and maximum E-wave velocity were statistically similar (81 +/- 13 vs. 85 +/- 12 msec; NS); and the average area of the forward transmitral pressure gradient associated with acceleration of early flow was significantly greater than the area of reversed gradient associated with deceleration of early flow (133 +/- 36 vs. 80 +/- 46 msec.mm Hg; p less than 0.025).(ABSTRACT TRUNCATED AT 400 WORDS)