Electroporation is a safe, efficient, and inexpensive method to transfer naked plasmid DNA into various tissues. For electroporation-mediated gene transfer to the mouse lung, a plasmid solution is delivered to the lungs via the trachea. Immediately after plasmid delivery, eight square wave pulses are delivered by two pregelled electrodes placed on each side of the chest. The optimal field strength is 200 V/cm, with a pulse duration of 10 ms each and a 1 s interval between pulses. High-level gene expression can be achieved within 24 h in all cell types in the lung, with very little inflammation and no apparent trauma.