Sirolimus (RAPA), a powerful immunosuppressor with a novel mode of action, has been promoted, as a non nephrotoxic drug. It is meant to allow a reduction in the previously suggested doses of calcineurin inhibitors, and in some cases replace them. The initial reports have suggested bone marrow depression (mainly thrombocytopenia) and dyslipidemia as the main side effects of this drug. We have reviewed 22 of our patients treated with RAPA since 1999 with doses varying from 2 to 5mg per day most of them (16 patients) received Mycophenolic Acid (MMF) as well, while others were on Azathioprin (AZA) (6 patients). The doses of MMF varied from 500mg to 2 Gm / day and those of AZA from 75 mg to 150 mg /day. Our results were as follows: No case of thrombocytopenia was found. Leucopenia (WBC< 3000/cc) was reported in 13.6% of patients. Anemia (Hct < 35%) was reported in 22.7%. Dyslipidemia was almost universal, necessitating the use of statins in most (56%). Seventy six percent of the patients had hypercholesterolemia (LDL > 115 mg%) and 68% had hypertriglyceridemia (TG > 150 mg%). However, a high incidence of supposedly rare complications were encountered despite the use of relatively small doses of RAPA: Pulmonary toxicity (9%), upper respiratory infection, URI (18%), edema (13.6%), arthritis and/or arthralgias (22.7%), diarrheas (27.2%) (more than one episode per patient), myalgias (13.6%), CMV reactivation (8%) , urinary tract infections UTI (9%) (more than one episode per patient), mouth ulcers (18%) that were found mainly in patients taking MMF and RAPA simultaneously. We conclude that our population has a different set of susceptibilities to RAPA and requires new modalities of RAPA prescription to suite it.