Recent growth studies in children suggest that there is no threshold for adverse effects from the universal exposure to inorganic lead. The biochemical mechanisms mediating low-level toxicity are unclear, but in several biological systems, lead alters calcium-mediated cellular processes and may mimic calcium in binding to regulatory proteins. Here we present evidence that lead stimulates diacylglycerol-activated calcium and phospholipid-dependent protein kinase, protein kinase C, partially purified from rat brain. Picomolar concentrations of lead are equivalent to micromolar calcium in kinase activation, so this regulatory enzyme is sensitive to the lead levels expected from current environmental exposure.