The present studies were undertaken to investigate the in vitro effects of mercuric chloride (HgCl2) and methylmercury chloride (CH3HgCl) on the uptake of [3H]alanine, [3H]phenylalanine, [3H]glutamic acid, [14C]alpha-methylamino-isobutyric acid, and Rubidium (86Rb), as well as on the activity of gamma-glutamyl transpeptidase (gamma-GTP) in rat brain microvessels. Similar patterns of inhibition of uptake by capillaries of amino acids and 86Rb were observed in the presence of both mercury compounds. Marked inhibition of uptake was seen at concentrations of 10(-5) and 10(-4) M of both compounds, but the uptake was not inhibited at concentrations less than 10(-5) M. Capillary gamma-GTP activity was not influenced by either HgCl2 or CH3HgCl, suggesting that this enzyme does not play any role in the transport of the amino acids studied in these experiments. The results indicate that the main toxic effect of mercury compounds is inhibition of amino acid transport. The concentration at which mercury exerts its inhibitory effect in this study is similar to that estimated to have been present in the brains of victims during the Minamata epidemic.