Low energy visible light (LEVL) irradiation has beenshown to exert some beneficial effects on various cell cultures. For example, it increases the fertilizing capability of sperm cells, promotes cell proliferation, induces sprouting of neurons, and more. To learn about the mechanism of photobiostimulation, we studied the relationship between increased intracellular calcium ( Life on earth is entirely dependent upon the interaction of sunlight with cells especially in plant photosynthesis (1). Sunlight also has medical benefits, which have been exploited for over thousands of years in ancient Egypt, India, and China in treating skin diseases, psoriasis, vitiligo, and even cancer (2). Recent observations show that even low energy visible light (LEVL) 1 can serve as a medical tool. For example, LEVL increases the rate of wound healing (3), enhances the fertilizing capability of sperm cells (4), and increases the rate of healing bone defects (5). In vitro studies have found that LEVL increases proliferation of cells as fibroblasts (6), keratinocytes (7), and lymphocytes (8) and induces the respiratory burst in neutrophils (9). The mechanism of photobiostimulation by LEVL is still unclear. It has been suggested that reactive oxygen species (ROS), which can be produced by photosensitization of endogenous cell chromophores such as cytochromes (10) [Ca 2ϩ ] i followed by myosin phosphorylation and cell contractions (26). Growth factors and hormones were shown to stimulate ROS production, which were dependent on [Ca 2ϩ ] i rise (27). The relationship between ROS and [Ca 2ϩ ] i has been suggested to involve the redox-sensitive transcription factor N, which was found to change [Ca 2ϩ ] i homeostasis in response to changes in the redox state of thiol groups (28). The kinetics that characterize the [Ca 2ϩ ] i elevation have been shown to be an important parameter determining the kind of signal that will be evoked. Livingston et al. (29) showed that high concentrations of oxidants (Ͼ50 M) caused a sustained increase in [Ca 2ϩ ] i , whereas a transient increase in [Ca 2ϩ ] i was observed following administration of a low concentration of oxidants. More than a 4-fold increase in the [Ca 2ϩ ] i level was obtained in photodynamic treatment of mouse myeloma cells that had been enriched with exogenous photosensitizers before illumination, whereas only a slight increase in [Ca 2ϩ ] i was observed in irradiated cells without exogenous photosensitizers (30).Only a few works have dealt with calcium/ROS changes following LEVL irradiation. In this study, we have investigated * The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.§ The article describes research performed by Ronit Lavi as partial fulfillment of the requirements for her Ph.D. degree at Bar-Ilan University. To whom correspondence should be addressed. Tel.: 972-3-5317797; Fax: 972-3-...