To date, no study has investigated the effects of bupropion (BP) in renal-impaired humans. This study aims to identify the pharmacokinetics of BP and metabolites in haemodialysis patients who smoke, determine whether haemodialysis affects BP and metabolite clearance, and suggest the BP dose in haemodialysis. The pharmacokinetics of BP and two of its major metabolites, hydroxybupropion (HB) and threohydrobupropion (TB) were studied in 8 smokers with ESRD receiving haemodialysis. Following a single oral dose of 150 mg bupropion hydrochloride sustained-release, blood samples were taken over 7 days, which were assayed using HPLC-mass spectrometry. Pharmacokinetic analysis was undertaken by non-linear regression using MWPharm. The BP results were similar to those for individuals with normal renal function. The metabolites demonstrated increased areas under the curve, indicating accumulation. Dialysis clearance of HB is unlikely. The results suggest significant accumulation of the metabolites in renal failure. Clarification of the clinical importance of the metabolites and toxic plasma levels is required. The effects of haemodialysis on BP and metabolites require further study. A dose of 150 mg bupropion every 3 days in patients receiving haemodialysis is more appropriate than the current manufacturer’s recommendation (in renal impaired patients) of 150 mg daily. A multi-dose study is required.