The plasma homocysteine (Hcy) concentration represents the balance between its entry and removal from the circulation. This understanding has stimulated efforts to elucidate the causes of hyperhomocysteinemia by measuring plasma Hcy turnover. However, these studies have been performed under steady-state conditions, which do not allow for conclusions about the type and severity of the metabolic blocks that cause metabolites to accumulate. Failure to appreciate this has led to some confusion in the literature dealing with whole body Hcy metabolism.