The decrease of the tryptophan fluorescence (Ex/Em = 282/331 nm) was used to monitor the kinetics of copper-mediated LDL oxidation. Cu2+ causes a concentration-dependent quenching of the LDL Trp-fluorescence, the maximum of about 22% suggests that 8-9 Trp residues (out of a total of 37) are accessible for Cu2+ ions. Decomposition of LDL tryptophan commences immediately after addition of Cu2+ and proceeds in two stages with quite different rates. At a molar ratio of Cu2+/LDL = 33:1 the LDL particle looses 1 Trp every 13.5 min in the initial slow phase and every 4.1 min in the subsequent rapid The second, stage temporarily coincides with the propagating lipid peroxidation. In the initial phase loss of Trp proceeds with a constant rate for up to 200 min depending on the copper concentration. Whereas lipid peroxidation accelerates after consumption of vitamin E, rate of Trp loss does not increase. Loading of LDL with vitamin E has also no effect on the initial rate of Trp loss. During the initial phase a loss of one Trp residue/LDL is accompanied by the loss of two alpha-tocopherols and the generation of two conjugated lipid hydroperoxides. The results suggest Trp residues play a role in initiating the lipid peroxidation process in the LDL particle. In such kinetic studies, precautions must be taken to avoid photodecomposition of LDL-Trp. The LDL vitamin E fluorescence (Ex/Em = 290/323 nm) does not interfere with the Trp fluorescence even at high concentrations.