The magnesium content of Saccharomyces cerevisiae was found to vary by up to fivefold at differing stages of batch growth and during growth in the presence of differing magnesium concentrations. Excess Mg was primarily sequestered in vacuoles. Mn2+-uptake experiments revealed that Mg-enriched cells had a markedly reduced capacity for Mn2+ accumulation. For example, after 6 h incubation in the presence of 50 mu M Mn2+, Mn levels were approximately twofold higher in cells previously grown in unsupplemented medium than in those from Mg-supplemented medium. These differences were further accentuated at higher Mn2+ concentrations and were not attributable to altered cell-surface charge or altered cell-surface Mn2+ binding. Cellular Mg status also influenced Mn toxicity towards S. cerevisiae. During exposure to 5 mM Mn2+ 50% reductions in the viability of cells with initial Mg contents of approximately 1400 and 2700 nmol (10(9) cells)(-1) occurred after approximately 1.6 h and 3.6 h respectively. In cells containing 3300 nmol Mg (10(9) cells)(-1) more than 75% viability was still maintained after 7 h incubation with 5 mM Mn2+. It is concluded that Mn2+ uptake and toxicity in S. cerevisiae are strongly influenced by intracellular Mg, possibly through Mg-dependent regulation of divalent-cation transport activity.