The photosensitizing effects of tetraphenylporphycene (TPPo) and light on HeLa cells, with emphasis on cell viability and the microtubular network, have been investigated. The survival of the cells incubated with TPPo was dependent on both drug concentration and light dose. The integrity of microtubules (MTs) was evaluated by immunofluorescence staining of alpha-tubulin. Interphasic and mitotic MTs were altered after 30 min of incubation with 5 microM TPPo followed by light irradiation. The degree of damage depended on light exposure time: 3 or 15 min corresponded to survival rates of approximately 50% or < 5%, respectively. Sublethal treatment led to the gradual accumulation of cells in metaphase, which caused an increase in the mitotic index (MI), with a maximum being found 6 h later. The number of cells in metaphase, as well as the MI, were within control values 24 h after sublethal photodynamic treatment. Lethal treatment provoked irreversible damage of interphasic and mitotic MTs. In addition, cell surface modifications such as bleb projections of the plasma membrane were also observed immediately after lethal treatment. It is concluded that both cellular structures, plasma membrane and MTs, constitute important targets for the phototoxic action of TPPo.