Hydroxychloroquine (HCQ) is an antimalarial agent with immunomodulatory effects. It is widely used in rheumatologic diseases, and has a very high efficacy/toxicity ratio. It is particularly important in the treatment of systemic lupus erythematosus (SLE) since it reduces new organ involvement and disease flares, and relieves skin and joint symptoms. Some patients develop hypersensitivity rash in response to HCQ. In such patients the drug is withdrawn and replaced by another medication. All the alternative medications for rheumatological patients are significantly more toxic than HCQ. We describe our initial experience of HCQ slow oral desensitization. All 4 patients who were recruited completed the procedure successfully without significant difficulty. Our results suggest that HCQ slow oral desensitization is safe, effective, and easy to perform.