The use of implantable neural prostheses activated by radiofrequency transmission requires that the materials in the device and the stimulation techniques are not injurious to neural tissue, particularly the neurons. In this report, we discuss our experiences in the search for safe stimulation techniques. Acute and chronic experiments have been performed to evaluate electrode design and materials and to observe the effects of various stimulus protocols on the blood-brain barrier and brain. Neural tissue underlying the stimulated and control electrodes has been examined with both light and electron microscopy. Observations up to the present time indicate that the charge per phase is the most relevant stimulus parameter although the importance of charge density and current density cannot be underestimated.