Sonogashira coupling between 3,5,3 0 ,5 0 -tetrabromo-[2,2 0 ]bithiophene and various terminal alkynes provides two-photon absorp-tion (TPA) chromophores 1–6, which possess electron donor (D) and/or acceptor (A) alkynyl substituents at 3(3 0) and 5(5 0) sites of the bithio-phene core. The up-converted fluorescence emission excited at 800 nm (Ti:sapphire femtosecond laser,w100 fs pulses) was used to determine the two-photon absorption cross-sections (s) of these compounds. The corresponding TPA cross-section (s) values ranging from 132 to 1120 GM (10 À50 cm 4 s photon À1) can be fine-tuned by the substitutents. The quadrupolar-type (A-p-D-p-A) chromophore 5 exhibits the largest s value (1120 GM) in CH 2 Cl 2 upon 800 nm excitation.