A 47-year-old Caucasian woman had a 3.5-year history of primary hypothyroidism treated with levothyroxine. Her levothyroxine dosage of 0.05 mg/day had been stable for the past 15 months. She was then prescribed raloxifene for prevention of osteoporosis secondary to early menopause. During the next 30 months, her levothyroxine dosage had to be gradually increased. The patient had been taking levothyroxine and raloxifene at the same time each day on an empty stomach. During the months of her levothyroxine dosage changes, however, she separated administration of levothyroxine and raloxifene by 12 hours; the patient then became hyperthyroid. Eventually, her levothyroxine needs decreased, and she returned to the same levothyroxine dosage she had taken before separating administration of the two drugs. These findings suggest that raloxifene decreased the absorption of levothyroxine when the two agents were coadministered. Assessment of causality using the Naranjo adverse drug reaction probability scale resulted in a possible association for this adverse event. Another published case report provides findings similar to our patient's experience. The possibility of a malabsorption interaction between levothyroxine and raloxifene is significant, as hypothyroidism is common among postmenopausal women-the same population that is the target of osteoporosis therapy with agents such as raloxifene. The mechanism by which raloxifene decreases levothyroxine absorption is unknown. Further investigation of this potential interaction is warranted. Until then, clinicians should be alert to the potential for an interaction between raloxifene and levothyroxine.