The well-known, defining feature of two-photon excitation (TPE) is the tight, three-dimensional confinement of excitation at the intense focus of a laser beam. The extremely small excitation volume, on the order of 1 μm3 (1 femtoliter), is the basis of far-reaching applications of TPE in fluorescence imaging, photodynamic therapy, nanofabrication, and three-dimensional optical memory. Paradoxically, the difficulty of detecting photochemical events in such a small volume is a barrier to the development of the two-photon-activated molecular systems that are essential to the realization of such applications. We show, using two-photon-excited fluorescence to directly visualize the excitation path, that confinement of both laser beam and sample solution within the 20 μm hollow core of a photonic crystal fiber permits TPE to be sustained over an extraordinary path-length of more than 10 cm, presenting a new experimental paradigm for ultrasensitive studies of two-photon-induced processes in solution. (Figure Presented).