The onset of mitral valve prolapse and its close correlate, the time of systolic click, vary considerably with different physiologic and pharmacologic interventions. In order to explain the mechanism responsible for these alterations, the effects of tilt and amyl nitrite inhalation on left ventricular dynamics and the time of the systolic click were studied by analyzing echocardiograms and simultaneously recorded phonocardiograms in 14 patients with mitral valve prolapse and mid-systolic click. The patients were studied in the supine position, with 40-60 degrees head-up tilt and after amyl nitrite inhalation. Computer analysis of the recordings was used to measure the left ventricular end-diastolic diameter, the click diameter (left ventricular diameter at the time of mid-systolic click), the maximal velocity of circumferential fiber shortening (max VCF), and the time interval between the first heart sound and systolic click (S1-X). With tilt and amyl nitrite, shortening of the S1-X interval b y an average of 44 and 87 msec, respectively, was observed. The click diameter, however, remained virtually constant with both maneuvers. Earlier prolapse after tilt was due to a decrease in the end-diastolic diameter from 5.03 +/- 0.74 to 4.50 +/- 0.68 cm (P less than 0.001) with no change in max VCF. Immediately after amyl nitrite, earlier prolapse was due to an increase of VCF in the preprolapse period, with max VCF increasing from 2.15 +/- 0.27 to 3.06 +/- 0.40 circ/sec (P less than 0.001), there being no change in the end-diastolic diameter up to this time. The constant click diameter indicates that the abnormal valve motion in this syndrome occurs at a critical left ventricular chamber size. Variations in the onset of prolapse are caused by changes in left ventricular end-diastolic dimensions and the velocity of circumferential fiber shortening in the preprolapse period.