Acanthosis nigricans has been associated with multiple endocrinopathies. The common denominator appears to be insulin resistance. Three patients are described (one woman and two men) who presented with hypothyroidism and acanthosis nigricans. All the patients had elevated insulin levels in the fasting state and in response to an oral glucose load. The mechanism for the resistance to insulin was a post-receptor binding defect or a structural abnormality in circulating insulin, since glucose tolerance and plasma cortisol, somatomedin, growth hormone, and insulin receptor concentrations in peripheral monocytes were all normal. Antibodies to insulin or the insulin receptor were absent. Neither insulin resistance nor acanthosis nigricans diminished following correction of the hypothyroidism. It is concluded that hypothyroidism may be associated with acanthosis nigricans, that hyperinsulinemia is a regular correlate of the skin disorder, and that treatment of the hypothyroidism does not resolve the hyperinsulinemia or the acanthosis nigricans.