Acute exposure to 1, 10 and 50 microM lead acetate solutions irreversibly decreased calcium currents in 21 of 30 nerve growth factor-differentiated PC12 cells. In five cells, however, calcium currents irreversibly increased following lead exposure. Lead was equally effective at blocking the peak and sustained components of the calcium current. These data suggest complex interactions between neurotoxicologically relevant lead concentrations and high-threshold calcium currents in mammalian cells. They provide further support for the notion that at least one target of lead's toxic action is the voltage-gated calcium channel.