Zinc is a potent inducer of the 72 kD heat shock protein (HSP72). In brain, pathological conditions such as ischemia and seizures increase extracellular zinc. The present study examines the effect of zinc on HSP72 expression in rat primary cortical astrocyte culture. Astrocytes were grown to confluence and exposed to zinc chloride in CO2-equilibrated Earle's buffered salt solution. Expression of HSP72 was examined using immunocytochemistry. HSP72 was induced with zinc concentrations of 5 to 100 microM after 4 h exposures, or 200 to 300 microM after 15 min exposures. At the lower concentrations expression occurred in small clusters of contiguous cells. At concentrations high enough to cause cell death, HSP72-positive astrocytes formed a continuous margin around patches of dead cells. These patterns of HSP72 expression are similar to the patterns seen after cerebral ischemia in vivo. Exposure to zinc at 100 microM for 4 h or 400 microM for 15 min caused greater than 90% cell death. Increases in extracellular zinc may contribute to HSP72 induction and astrocyte death under ischemia and other pathological conditions in brain.