Carbon based electrodes are widely used for in vivo and in vitro electrochemical studies. In particular, monoamine neurochemistry has been investigated using carbon microfibre electrodes. Similarly, glassy carbon (GC) is the preferred material for many biochemical applications, such as electrochemical detection in chromatography. More recently, boron doped diamond (BDD) has been utilized for biosensing, as its carbon sp(3) structure is expected to provide better resistance to analyte fouling. However, the main factor limiting the use of electrochemical sensors for biological studies is the effect of the biological matrix. Indeed, in vivo or in situ measurements expose the sensor to a complex matrix of proteins, which adsorb on the sensing surface and interfere with the electrochemical measurements. Here, we compare the performance of three carbon based electrodes: GC, GC with low surface oxides and BDD. The redox species ruthenium(III) hexaammine (outer-sphere), ferrocyanide (surface sensitive) and the biologically significant dopamine have been investigated in protein and blood-mimicking matrices. Cyclic voltammetry and electrochemical impedance spectroscopy have been used to examine the effect of spectator molecules and reaction products on electrode mechanisms. Our results show that BDD generally exhibits the best performance for most conditions and reactions and should therefore be preferred for measurements in biologically fouling environments. Furthermore. surface oxides seem also to improve resistance of the GC electrode to biofouling. (C) 2010 Elsevier Ltd. All rights reserved.