A tandem combinatorial reaction of four acyclic, colorless compounds (two α-aminoketones and two diones; one polar and one nonpolar for each) in aqueous solution (30 mM each, 60 °C, pH 7, 24 h) containing lipid vesicles and with or without quinones and solar illumination affords a distribution of up to 538 porphyrins in 1.6–3.9% overall yield. The reactions leading to the porphyrins can occur in either or both the aqueous phase and the hydrophobic membrane of the vesicles. The porphyrins encompass a broad range of polarity and partition in the aqueous-lipid medium. Two fractions obtained by size-exclusion chromatography include porphyrins associated with the lipid vesicles and porphyrins in the aqueous phase. The porphyrins in both phases are photoactive as demonstrated by fluorescence quantum yield measurements (Φ_f ∼ 0.07–0.08) and by the Krasnovsky reaction (a photosynthetic-like process). The constituents of the Krasnovsky reaction employed here are methyl red, ascorbic acid, and 2,6-dichlorophenolindophenol. Illumination of the two porphyrin-containing samples (aqueous phase or vesicles) in the presence of the Krasnovsky constituents results in the reduction of methyl red and oxidation of ascorbic acid. Thus, the overall process transforms a colorless aqueous suspension via four stages (two combinatorial reactions, oxidation, physical partitioning) to photoactive porphyrins in distinct venues. The process may provide a model for the origin of pigments that enable proto-photosynthesis.