PL-arginine cardioplegia decreases biochemical markers of myocardial damage and oxidative stress in patients with normal left ventricular function. We investigated the effects of L-arginine supplemented cardioplegic arrest in patients with reduced ejection fraction. Fifty-three adult patients with left ventricular ejection fraction <35% undergoing elective coronary artery bypass surgery were randomised to receive blood cardioplegia with or without L-arginine. Following cardiopulmonary bypass, measured endpoints were cardiac troponin-I concentration at 12 and 24 hours, coronary sinus concentrations of malondialdehyde and superoxide dismutase activity at five and 15 minutes, lactic acid flux at one, five and 15 minutes and left ventricular systolic and diastolic function after protamine administration. There were no differences in cardiac troponin-I between groups. Malondialdehyde was lower in the L-arginine group, 0.28 ± 0.12 vs 0.48 ± 0.32 (5 minutes) and 0.31 ± 0.14 vs 0.38 ± 0.15 nmol.ml(-1) (15 minutes) (P=0.0004). Superoxide dismutase activity was higher in L-arginine group, 229 ± 87 vs 191.3 ± 68 (5 minutes), 229 ± 54 vs 198 ± 15 nmol.minute(-1).m(l) (15 minutes) (P=0.005). Lactic acid flux was lower in L-arginine group, 0.15 ± 0.23 vs 0.48 ± 0.32 (1 minute), 0.08 ± 0.19 vs 0.38 ± 0.31 (5 minutes) and -0.15 ± 0.13 vs 0.26 ± 0.30 mmol.l(-1) (15 minutes), (P=0.0003). There was no difference in left ventricular systolic function. The mitral annular tissue Doppler inflow (e') velocity during early diastole improved in the L-arginine group following cardiopulmonary bypass (control 4.2 ± 1.9 cm.s(-1) to 3.6 ± 1.2 cm.s(-1) vs L-arginine 3.8 ±1.2 cm.s(-1) to 4.6 ± 1.4 cm.s(-1)) (P=0.018). In patients with reduced ejection fraction, L-arginine supplemented cardioplegic arrest did not affect postoperative cardiac troponin-I levels, but attenuated cardiac cellular peroxidation and improved early left ventricular diastolic function.