BACKGROUND: In order to determine the possible origins of undetectable EPO profiles in athletes' urine, we analyzed the data obtained from a large number of official anti-doping urine tests aimed at detecting recombinant erythropoietin. The following variables were considered as potential causes for lack of EPO detection: athlete's gender, competition effect, urine specific gravity as well as possible usage of proteasic adulterants to evade doping detection. RESULTS: Statistical analyses indicated that undetectable EPO profiles were clearly related to urine properties such as low EPO concentrations or extreme specific gravities. The addition of very small quantities of protease was shown to remove all traces of EPOs in urine. This finding led to the development of a simple, specific and sensitive test that reveals proteasic activity based on albumin digestion. CONCLUSIONS: Urine characteristics clearly affect the detectability of an EPO profile. At the same time, addition of anti-proteases prevents the adulteration of urine. These two findings have clear practical implications with regards to the timing of urine collection as well as the entire anti-doping control procedure.