We sought to determine if failure to thrive in pediatric patients with the human immunodeficiency virus could be explained based on endocrine dysfunction. Fourteen human immunodeficiency virus-infected pediatric patients, all of whom had adequate nutritional status, underwent endocrine evaluation. Growth hormone and cortisol responses to glucagon stimulation were adequate. Despite this, eight of the 12 subjects had low somatomedin C levels. Although all patients were clinically and biochemically euthyroid, 36% (5/14) demonstrated elevated baseline and peak thyrotropin levels in response to thyroid releasing hormone, suggesting a state of compensated hypothyroidism. Although the importance of these findings is unclear, it is possible that subtle alterations of thyroid regulation may contribute to failure to thrive in some pediatric patients infected with human immunodeficiency virus and may represent a potentially correctable defect.