Aldehyde-induced side effects limit the clinical usefulness of bioprosthetic heart valves. Treatment of aldehyde-fixed pericardium with L-glutamic acid at pH 3.5 and storage in a nontoxic, bacteriostatic solution resulted in a lower degree of calcification in 63-day subcutaneous implants in rats (13.3 +/- 2 mg calcium per gram dry weight of tissue), as compared with commercially available tissue (169 +/- 24 mg/gm, p less than 0.05). Endothelial cells died within 1 day after seeding on the commercial tissue; however, considerable endothelial cell proliferation was measured, even 14 days after seeding on L-glutamic acid-treated pericardium. Improved biocompatibility of this alternative treatment may be due to stable chemical binding of free, reactive aldehyde groups.