Insertable microelectrode arrays can be used to activate neurons or to sense neural signals for use in prosthetics. The relationship of the microelectrodes to the neurons is determined by random alignment and by biocompatibility. Issues that determine the biocompatibility of insertable microelectrode arrays were investigated. Arrays were implanted into the cortex of rabbit brain and fixed to the skull. Following six-month survival, neuron density as a function of distance from the shafts of the arrays was measured to assess destruction of neurons. Results from a limited number of tests indicated that there was minimal tissue response along the sides of the shafts when shafts were well sharpened, had sufficiently small tip angles, and were clean. Tissue was usually more reactive at the tips of the shafts. It was concluded that silicon microshafts of appropriate shaft and tip design were biocompatible along the sides of the shaft, but that relatively severe reactions could be anticipated at the tips. Recording or stimulation sites should be located away from the tips on the sides of the shafts for better coupling with individual neurons. Measurement of neuron density as a function of distance from the shafts was a sensitive and quantitative technique for assessing biocompatibility. Additional measures such as glial density as a function of distance from the shafts, and incidence of microhematoma formation were proposed.