Among 772 kidney transplant recipients in two centers 25 patients developed Kaposi's sarcoma (KS) (3.2 %). The twenty-two of 25 recipients with regular follow-up records were compared for predisposing factors with another group of 22 renal transplant recipients. All patients received cyclosporine (CsA), azathioprine, or mycophenolate mofetil and steroids; patients who received cadaver donor organs additionally received antilymphocyte globulin for induction. KS was diagnosed at a mean of 25.8 months after transplantation. The male to female ratio; mean age; mean follow-up period; hepatitis B, hepatitis C, cytomegalovirus status; and other infection rates were similar in the two groups. Some HLA-DR antigens were detected only in patients with KS. All patients had mucocutaneous involvement, which was multiple in 54.5 %. Visceral involvement, and lymph node involvement, or both was detected in seven patients. First-line treatment was to stop CsA and reduce the doses of the other drugs. Three patients underwent additional surgical excision. Fourteen (63.6 %) patients experienced complete remissions, including six who required additional chemotherapy or radiotherapy after incomplete or lack of responses to first-line treatment. Two patients died with functioning grafts due to generalized KS. Seven patients returned to hemodialysis at a mean of 36 months after the diagnosis of KS. No significant predisposing factor was observed other than the prevalence of specific HLA-DR antigens. Chemotherapy or radiotherapy should be initiated for patients with multiple, diffuse, and rapidly progressive lesions or organ dysfunction in addition to withdrawal of CsA and tapering of other drugs. Generalized KS displays the poorest prognosis.