The aggregation status of chlorophyll a (Chl a) and the ability of four cyclodextrins, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD), heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DIMEB), and heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TRIMEB), to solubilize the pigment in the complete cellular medium RPMI 1640 was estimated by means of UV-Vis absorption and static resonance light scattering (RLS) measurements. The results indicate that the pigment interacts with cyclodextrins in the cellular medium differently to that observed in water. The cytotoxic and phototoxic activity of these complexes towards human leukemia T-lymphocytes (Jurkat cells) was tested by means of experiments aimed to discriminate between the intrinsic toxicity and the toxicity induced by light. The overall data indicate that the HP-beta-CD is the cyclodextrins having the best characteristics to form with Chl a a potential supramolecular system for the photodynamic therapy.