Immunosuppressive effects of the minor component of the terrestrial solar spectrum, UV radiation, have been substantiated over the past several years. This raises the question of what influence the dominant part of the solar spectrum—visible and IR light—would have on the human immune system. In the present randomized, placebo-controlled double-blind study a small area of the body surface of volunteers was irradiated with polychromatic light (480–3400 nm), simulating the significant part of the terrestial sunlight irradiance spectrum and its power density. An average 2.5-fold to three-fold increase in spontaneous and phytohemagglutinin-induced DNA synthesis in peripheral blood lymphocytes (Lym) was revealed at 0.5–24 h after irradiation at a therapeutic dose (12 J/cm²) in subjects with low preirradiation levels of both processes. The in vivo findings were echoed in parallel in vitro experiments, when blood drawn from the same subjects was directly irradiated (2.4 J/cm²), or when the irradiated blood was mixed 1:10 with nonirradiated autologous blood to model events in the circulation following transcutaneous blood photomodification. Our data suggest that exposure of the human body to polychromatic visible IR light may photomodify blood in the dermal vasculature of the irradiated area to lead to an immediate transfer of the light-induced effects to Lym of the entire circulating blood, which can result in modulation of Lym functional state at the systemic level.