1. The effects of inorganic Hg2+ and methylmercuric chloride in the ionic currents of cultured hippocampal neurons were studied and compared. We examined the effects of acute exposure to the two forms of mercury on the properties of voltage-activated Ca2+ and Na+ currents and N-methyl-D-aspartate (NMDA)-induced currents. 2. High-voltage activated Ca2+ currents (L type) were inhibited by both compounds at low micromolar concentrations in an irreversible manner. Mercuric chloride was five times as potent as methylmercury in blocking L-channels. 3. Both compounds caused a transient increase in the low-voltage activated (T-type) currents at low concentrations (1 microM) but blocked at higher concentrations and with longer periods of time. 4. Inorganic mercury blockade was partially use dependent, but that by methylmercury was not. There was no effect of exposure of either form of mercury on the I-V characteristics of Ca2+ currents. 5. Na(+)- and NMDA-induced currents were essentially unaffected by either mercury compound, showing only a delayed nonspecific effect at a time of overall damage of the membrane. 6. We conclude that both mercury compounds show a relatively selective blockade of Ca2+ currents, but inorganic mercury is more potent than methylmercury.