To understand endocrine function and to determine which endocrine systems are likely to be affected, 6 patients with mitochondrial encephalomyopathies were studied. Three patients had myoclonus epilepsy and ragged-red fibers, and the other 3 patients had mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. Clinically, short stature (5/6), amenorrhea (2/3), impotency (3/3), and poor development of secondary sexual characteristics (4/6) were noted. The endocrinological studies including triiodothyronine, tetraiodothyronine, thyrotropin, adrenocorticotropin, cortisol, parathyroid hormone and blood sugar were normal. However, there were low serum concentrations of estradiol (2), and progesterone (2) in 3 female patients. Two patients (1 man and 1 woman) had growth hormone deficiency and 1 had low testosterone level. Hypothalamopituitary dysfunction was confirmed after a series of stimulation tests. We conclude that patients with mitochondrial encephalomyopathies are common to have gonadal dysfunction. Although target organ may play a role, hypothalamopituitary lesion may be responsible for this abnormality.