During cell cycle progression, cells increase in size and must pass a size-dependent checkpoint prior to mitosis. Once a cell has passed this restriction point, it is committed to one cycle of division. Swelling could act as a proliferative signal through activation of cytoplasmic signalling cascades and gene transcription [1]. Mitogen activated protein kinases (MAPK) are central components of the signalling pathways involved in cell cycle progression. Previous studies from this laboratory have demonstrated a rapid early increase in ERK-1,2 activity in chick myocytes following hyposmotically-induced swelling [2]. Such MAPK activation could provide a link between swelling and proliferation. Embryonic chick hearts were removed at day 10 of development; myocytes were isolated enzymatically and maintained in culture. These cells may undergo at least one further cycle of cell division before terminal differentiation. Reducing extracellular osmolarity causes a significant increase in cell volume; e.g. cell volume increases to ~140% in hyposmotic solution (180 mosmol/l), before regulatory volume decrease occurs [2]. In this study, volume was perturbed by alteration of the extracellular osmolarity (150-400 mosmol/l by omission or addition of mannitol from the culture medium) for up to 48 hours. Cell proliferation was monitored by spectrophotometric assay of the number of viable cells [3]. Statistical comparison of absorbance between experimental groups was performed using one-way ANOVA and post-hoc Tukey tests; significant differences were accepted if p<0.05. Our results demonstrate that cells exposed to hyposmotic media (200mosmol/l) showed a rapid early increase in proliferation, compared to control cultures (Fig. 1). The absorbance was significantly increased, relative to controls at 24 h (0.172±0.071; n=9 wells cf. 0.001±0.004; n=6) and 48 h (0.300±0.095; n=12 cf. 0.048±0.033; n=8). In contrast, cells incubated in hyperosmotic media (400mosmol/l; n=2 experiments) failed to proliferate. Similarly, cells treated with the MEK inhibitor PD98059 (50μM) also failed to proliferate in hyposmotic media (n=2 experiments). This study establishes a link between hyposmotically induced cell swelling and an increase in cell proliferation, and suggests a role for ERK1,2 signalling in swelling-induced mitosis. These data demonstrate that inducing changes in cell size may accelerate or halt progression through the cell cycle.