Endocrine and metabolic abnormalities are common in human immunodeficiency virus (HIV) disease and have been attributed to both the disease and its treatment. Other risk factors and behaviors may also be important. Approximately 28% of new HIV infections occur in users of injection drugs, such as opiates. We focus on the effects of opiates on multiple endocrine systems and their potential to contribute to the metabolic and endocrine problems in HIV. Opiate use has been associated with hypogonadism, adrenal dysfunction, reduced bone mineral density, and growth-hormone abnormalities. In addition, some studies have suggested abnormalities in glucose and lipid metabolism among opiate users. Although much of the evidence should be viewed as preliminary, these potential abnormalities should be kept in mind when treating opiate-dependent patients infected with HIV.