The dialysis clearance of methylguanidine (MG) was found to be lower 'in vivo' than 'in vitro' and to decrease during a haemodialysis. Its protein binding, which rises as the plasma pH rises during haemodialysis, accounts for its dialysis behaviour. The low dialysis clearance of MG 'in vivo' explains why the post dialysis percentage decrease in its plasma levels is lower than that of urea (U) and of creatinine (CR). The slow transfer of MG from tissue during dialysis, shown by direct measurements on plasma and muscle tissue of anuric dogs, accounts for its high plasma rebound level after haemodialysis. Rebounds after peritoneal dialysis were lower and the plasma MG levels 12 hr after the termination of the two dialysis procedures were not different. The dialytic behaviour of MG is different from that of U and of CR which have similar molecular weights and the conclusions drawn from the behaviour of the latter two metabolites cannot be applied to MG. On the contrary, the removal of MG from body fluids of uraemic patients by dialysis is equal with peritoneal dialysis and with the various haemodialysis schedules that ensure good clinical results, while leaving plasma U and CR concentrations in a high range.