A subset of 12 Kirtland's snakes, Clonophis kirtlandii, that died at the Louisville Zoological Garden (Louisville, Kentucky) between 1998 and 2004 were evaluated by one pathology service due to a historic high prevalence of thyroid gland enlargement and mortality. Subjective enlargement of the thyroid (goiter) was noted at necropsy in eight of 12 cases, whereas microscopic thyroid lesions were observed in all 12 snakes. Ten of 12 cases also were noted to have pulmonary, coelomic, and intravascular proteinaceous fluid accumulation interpreted as a possible hyperviscosity-like condition. This is presumed to be secondary to metabolic derangements associated with the thyroid disease. Antemortem thyroid hormone testing and confirming and better characterizing the suspected hyperviscosity-like condition via hematologic evaluation and protein electrophoresis was not performed due to small patient size. No sex predilection was observed, and the range of time affected snakes were in captivity before death was 14 to 56 months. The high prevalence of goiter and thyroid disease may be due to suboptimal dietary iodine, other nutritionally deficiencies, exposure to goitrogenic substances, exposure to and bioaccumulation of endocrine-disrupting contaminants from the environment, genetic predisposition, or a combination. Supplementation with iodine was attempted in some snakes in various ways but was generally unsuccessful.