Anesthesia induces significant caspase-3 activation in the developing occipital cortex of 5-day-old piglets. The sensitivity of occipital cortices in piglet brains to general anesthesia is quantified as the number of caspase-3-positive cells/mm3 in layers II and IV. The density of caspase-3-positive neurons in “true” control was minimal in the parietal cortical regions. Although a somewhat higher degree of labeling occurred in sham control (exposed to continuous fentanyl infusion, 15 μg/kg/h), the difference from labeling in “true” control was not statistically significant. The combination of isoflurane (0.55-vol%), N2O (75 vol-%), and midazolam (1 mg/kg, i.m.) caused a significant increase in caspase-3 labeling as compared to that in “true” and sham controls (*, P < 0.001, and †, P < 0.001, respectively) (n = 1 piglet per condition, n = 4–5 sections per brain region).