The mouse microphthalmia (mi) gene encodes a basic-helix-loop-helix-zipper protein whose mutations may lead to loss of pigmentation in the eye, inner ear and skin, and to reduced eye size and early onset deafness. Mice with mutations at mi serve as models for human pigment disturbances in skin and eye that may be combined with sensorineural deafness. We have now obtained cDNA and genomic clones of the human homolog of mouse mi, identified a restriction fragment length polymorphism in the gene, and mapped the gene by somatic cell hybrid and fluorescence in situ hybridization techniques to a region of human chromosome 3 that shows a disrupted syntenic conservation with the region on mouse chromosome 6 to which mi maps. These studies will help to verify if any of the hereditary pigment disturbances in humans are due to mutations in this gene.