ABSTRACT In order to investigate the effects of a permanent increase in cellular H2O2 on cation homeostasis we have utilized a T-DNA insertion mutant of the Arabidopsis CATALASE 2 gene. This mutant (cat2-1) exhibits 20% of wild type leaf catalase activity and accumulates more H2O2 than wild type under normal conditions. In addition to reduced size, pale green color and great reduction in secondary roots, the cat2-1 mutant exhibited increased sensitivity to H2O2 , NaCl, norspermidine, high light and cold stress. On the other hand, the germination of the cat2-1 mutant is more tolerant to lithium than that of wild type. This novel phenotype cannot be explained by changes in lithium transport. Actually, the uptake of lithium (and of other toxic cations such as sodium and norspermidine) is increased in the cat2-1 mutant while K+ levels were decreased. Lithium tolerance of this mutant seems to result both from insensitivity to the inhibitory ethylene induced by this cation and from reduced capability for ethylene production. Accordingly, induction by ethylene of responsive genes such as etr1-1 and ein3-3 are lithium tolerant and inhibition of ethylene biosynthesis with 2-aminoisobutyrate protects against lithium toxicity. Microarray analysis of gene expression indicates that the expression of genes related to cation transport and ethylene synthesis and perception was not altered in the cat2-1 mutant, suggesting that H2O2 modulates these processes at the protein level. These results uncover a cross-talk between oxidative stress, cation homeostasis and ethylene.