Unexpectedly prolonged activated partial thromboplastin times (APTTs) were noted in several patients with chronic renal insufficiency and a history of intravenous drug abuse. Deposits of polyvinylpyrrolidone (PVP), an excipient in one oral methadone solution used in opioid maintenance programs, were found in renal biopsies. One case is described in detail, and this is followed by a summary of findings in 11 other patients and the results of an in vitro experiment in which plasma was spiked with PVP at increasing concentrations. APTTs measured with STA PTT automate (Stago) were prolonged in all patients and in spiked samples, whereas supplemental coagulation parameters and APTTs measured with HemosIL SynthAsil or Actin FSL (Siemens) were within reference intervals. These results indicate that interference with APTTs by PVP is reagent-dependent. We suggest that a prolonged APTT should raise the suspicion of PVP deposit-associated kidney disease in patients with chronic renal failure and a history of intravenous drug abuse.