Systemic administration of 13-cis-retinoic acid caused a reduction of acinar tissue in the hamster meibomian gland. Histologic examination of treated meibomian gland tissue revealed a thickening of gland ductal epithelium and a decrease in the numbers of mature lipid-laden acinar cells. Morphometric analysis showed a reduction of up to 75% in mean volume of meibomian acinar tissue from animals fed a high dose of 13-cis-retinoic acid. Clinical observations in these animals included alopecia and weight loss. Ocular complications included crusting of the eyelid margin and the external surface of the lid and erythema of the conjunctiva. The model supports previous observations by the authors that systemic 13-cis-retinoic acid affects meibomian gland structure in a laboratory animal. The ocular side effects described in this model suggest that future functional studies may yield important insights into the complex relationship between meibomian gland morphology and function, and events on the ocular surface.