This study was conducted to determine whether Al, a metal without redox capacity in biological systems, can stimulate Fe(2+)-supported lipid peroxidation through changes in the physical properties of membranes. The capacity of Al to stimulate Fe(2+)-induced lipid peroxidation in liposomes was characterized measuring the formation of 2-thiobarbituric reactive substances (TBARS) and the disappearance of select fatty acids. Al (12.5-250 microM) promoted Fe(2+)-initiated lipid peroxidation in a dose- and time-dependent manner. The effect of Al was favored by decreasing the pH of the medium and by increasing the negative charge of liposomes. These results suggest that Al3+ is the species involved in the effect and that the binding of Al to the membrane is an important step in Al-mediated stimulation of Fe(2+)-supported lipid peroxidation. The stimulatory effect of Al3+ on TBARS production was significantly correlated (P < 0.02) with its capacity to promote liposome aggregation (r2 = 0.90), 5(6)-carboxyfluorescein release (r2 = 0.87), and liposome fusion (r2 = 0.90). Al promoted the immobilization of a spin probe (16-doxyl-stearic acid) incorporated in the liposomal membranes, indicating that Al causes fatty acid chain packing. The present results indicate that Al can stimulate Fe(2+)-supported lipid peroxidation through binding to the membrane and promotion of changes in the arrangement of membrane lipids including packing of fatty acids that will facilitate the propagation of lipid peroxidation.