Sulindac is a nonsteroidal anti-inflammatory agent that has been associated with serious adverse reactions. We saw four patients with reactions associated with sulindac. Our patients, one of whom died, had high temperatures and involvement of one or more organs, including the skin, liver, CNS, lymph nodes, bone marrow, and lungs. Eight similar previously reported cases also are summarized. In view of these cases of sulindac-induced toxicity, six of which were proved unequivocally by drug rechallenge, we suggest that physicians be cautious in prescribing this agent.