Hairless guinea pigs were born in a closed colony of Hartley guinea pigs. At birth, hairless guinea pigs were smaller than littermates, had wrinkled skin and stunted vibrissae. The most striking abnormality histologically was distension of the upper portion of the pilary canal with thickening of the epidermis. Hairlessness resulted from production of abnormal hair shafts. Preliminary work indicated that in addition to hairlessness, the guinea pigs were athymic or hypothymic. Initial immunologic studies showed that the guinea pigs also were agammaglobulinemic. Animals that survived the weaning period died of infections that are usually associated with immunodeficiencies, such as systemic cytomegalovirus, systemic balantidiasis and Pneumocystis carinii pneumonia.