Cellular activation after ligand-receptor interactions includes rapid polymerization of actin, and, in T lymphocytes, the concomitant lateral redistribution of surface receptors and of cytoskeletal actin. Cytochalasin E specifically depolymerizes filamentous actin (F-actin), and increased proliferation of resting T cells from old but not young mice. This suggested an age-related increase in F-actin which could impair lymphocyte functions. The F-actin content of resting (GO) and stimulated T lymphocytes from spleens of C57BL/6 mice was quantitated using a fluorescein-like fluorophore, Bodipy, conjugated to phallacidin which binds only to F-actin. Flow cytometric analysis showed that baseline levels of relative F-actin content were significantly increased in resting cells from aged mice (24-25 mo). Activation of Go T lymphocytes with Concanavalin A produced an immediate (within 60 sec.) increase in F-actin in cells from old mice and it returned to baseline levels within 2 min.; no further increase occurred for up to 40 min. In contrast, F-actin levels in cells from young mice (4-6 mo.) began to increase within 2 min. after activation and continued to rise for up to 50 min. These differences in F-actin content and polymerization kinetics may result in impairment of cytoskeletal functions and be related to the age-associated alterations in signal transduction in T lymphocytes from older individuals. A comprehensive review of the topic, Chronobiology and Aging, was written. This was requested by the associate editor of the Journal of the American Geriatrics Society.