The performance of five tetrapyrrole molecules as sensitizers in regenerative solar cells was evaluated. The tetrapyrroles form two sets. One set contains three meso-substituted porphyrins that differ only in the nature of their surface-binding tether: isophthalic acid, ethynylisophthalic acid, or cyanoacrylic acid. The other set includes the ethynylisophthalic acid tether attached to porphyrin, chlorin, and bacteriochlorin macrocycles, which contain zero, one, and two saturated pyrrole rings, respectively. Incident photon-to-current efficiency was measured for each sensitizer loaded onto a mesoporous TiO2 semitransparent electrode in a solar cell. The porphyrin bearing the cyanoacrylic acid tether gives the largest peak and integrated (350-900 nm) photocurrent density of the five tetrapyrrole molecules. For this sensitizer, a quasi-monochromatic power conversion efficiency of 21% was obtained at the Soret maximum (450 nm), alone, with a fill factor of 0.69. To elucidate the molecular origins of the effects of tether and macrocycle reduction on photocurrent production, the measured redox potentials and optical absorption spectra were analyzed in terms of the characteristics (energies and electron-density distributions) of the frontier molecular orbitals obtained from density functional theory calculations. Additionally, first-principle simulations were performed for the production of photocurrent by hypothetical planar and actual mesoporous films of each sensitizer under AM 1.5 solar irradiation. Collectively, the findings give fundamental insights into the factors that govern the observed differences in photocurrent production characteristics for the five tetrapyrrole sensitizers. In addition, the results provide a framework for further tuning of the properties of these molecules and related sensitizers to enhance solar-cell performance.