Ascorbate-deficiency leads to extensive oxidative damage of proteins and protein loss in the guinea pig tissue microsomes as evidenced by sodium dodecyl sulfate polyacrylamide gel electrophoresis, accumulation of carbonyl, bityrosine as well as by tryptophan loss. Oxidative damage is reversed by ascorbate therapy. Oxidative damage in ascorbate deficiency also leads to lipid peroxidation in guinea pig tissue microsomes as evidenced by accumulation of conjugated dienes, malondialdehyde and fluorescent pigment. Lipid peroxides, disappear after ascorbate therapy but not by vitamin E. The observations substantiate the previous in vitro findings that ascorbate specifically prevents oxidative degradation of microsomal membranes. The results indicate that vitamin C may exert a powerful protection against degenerative diseases associated with oxidative damage and play a critical role in wellness and health maintenance.