Carbon nanotube transistors show tremendous potential for electronic detection of biomolecules in solution. However, the nature and magnitude of the sensing signal upon molecular adsorption have so far remained controversial. Here, the authors show that the choice of the reference electrode is critical and resolves much of the previous controversy. The authors eliminate artifacts related to the reference electrode by using a well-defined reference electrode to accurately control the solution potential. Upon addition of bovine serum albumin proteins, the authors measure a transistor threshold shift of -15 mV which can be unambiguously attributed to the adsorption of biomolecules in the vicinity of the nanotube.