Previously, we have reported on the selective accumulation of an atrial-like myosin light chain-1 (ALC1) in different forms of human ventricular hypertrophy. The present study involves the determination of ALC1content in a control group and in patients with aortic stenosis or insufficiency before and 56 ± 23 months after valve replacement and compares the hemodynamic and angiographic parameters. ALC1was quantified densitometrically after two-dimensional electrophoretic resolution of biopsy specimens from the left ventricle and was expressed in percent of total ventricular light chain-l. The mean ALC1content was 11.2 ± 9.2% in preoperative aortic stenosis and 4.5 ± 1.4% in aortic insufficiency, both being significantly (p<0.001) higher than the control value of 0.3 ± 0.3%. After valve replacement, mean ALC1content was lower than before, 4.2 ± 3.3% (p<0.05) in stenosis and 3.4 ± 3.1% (p=NS) in insufficiency. Left ventricular systolic pressure yields a significant (p<0.01) linear correlation (r=0.45) with the ALC1content in all preoperative and postoperative patients. Patient group averages of ALC1content correlate directly with left ventricular systolic and end-diastolic pressure and wall thickness (r=0.94–0.98) and, in an exponential fashion, with peak systolic circumferential wall stress (r=0.98) but not with muscle mass or any other parameter. The ventricular ALC1binds to myosin in proportion to its occurrence in the myocardium. The content of the endogenous ventricular light chain-1 did not change under pathological hemodynamics. The response in expression of the ALC1to pressure and volume overload suggests an adaptational process. This seems to be confirmed by its lower content in the postoperative patient groups with improved hemodynamic parameters. (Circulation Research1992;70:1035–1043)