The purpose of this study was to determine whether high voltage pulsed electrical stimulation reduces microvascular permeability to plasma proteins in a simulation of acute edema. Fourteen male golden hamsters were anesthetized and prepared for fluorescence microscopy of the cheek pouch. Intravenous fluorescein-labeled dextran (MW 150,000) served as a tracer of plasma proteins. Protein leaks from the microvessels were quantified every 5 minutes for a 25-minute baseline period and again after a 5-minute superfusion with 10(-5)-M histamine. High voltage stimulation (HVS) was applied simultaneously with the histamine to the vascular bed of the treatment animals in a dosage of 10, 30, or 50 V; the control animals received no electrical stimulation. Histamine increased microvessel leakiness in all groups, but the number of posthistamine microvessel leaks was significantly less in animals that received a 30- or 50-V dose of HVS than in the control animals or those that received a 10-V dose. The study results suggest that at intensities greater than a threshold dose, HVS reduces microvessel leakiness. Reduced microvessel leakiness may be one mechanism by which HVS retards edema formation.