In this work we present a modified yeast two-hybrid bioassay for the highly sensitive detection of protein-protein interactions, based on the electrochemical monitoring of β-d-galactosidase reporter gene activity, using p-aminophenyl-β-d-galactopyranoside (PAPG) as a synthetic substrate. In a model system, the sensitive detection of 17-β-estradiol was achieved at concentrations as low as 10 - 1 1 M (approx 2 pg/ml) by monitoring 17-β-estradiol receptor dimerization after exposure to 17-β-estradiol. The sensitivity of this system was higher than that of standard optical methods by three orders of magnitude.