Two carboxylate-substituted, fluorescent (Phi = 0.08), water-soluble poly(p-phenyleneethynylene)s (PPE) and a water-soluble model compound were exposed to a series of proteins and bovine serum. While the anionic PPEs do not have any specific binding sites, they form stable complexes with histone, lysozyme, myoglobin, and hemoglobin. The complex formation was evidenced by fluorescence quenching. Bovine serum albumin does not quench the fluorescence of the PPEs but enhances it, probably due to its surfactant character. These results imply that the use of charged conjugated polymers as biosensors, while an attractive proposition, has to take into account strong nonspecific interactions between conjugated polymers and the host of proteins that is found in cells and complex biological fluids.