In this study we provide evidence that the protein kinase C (PKC)-θ isoenzyme is recruited on to the mitotic spindle in dividing murine erythroleukaemia (MEL) cells and associates specifically with centrosome and kinetochore structures. None of the other PKC isoenzymes (-α, -δ, -ε, -µ and -ζ) expressed by MEL cells shows this localization on the mitotic spindle. An identical subcellular distribution of PKC-θ is also observed in dividing murine P3 myeloma cells and human LAN-5 neuroblastoma cells, indicating that this PKC isoenzyme interacts with the mitotic apparatus in mammalian cells. In phorbol-ester-treated non-growing MEL cells, a rapid change in the intracellular distribution of PKC-θ occurs. Under these conditions, PKC-θ is translocated from the nuclear to the cytosolic cell compartment, an event that is accompanied by phosphorylation of the PKC-θ molecule and is followed by its down-regulation. The recovery of cell growth capacity results in the concomitant reappearance of PKC-θ. Furthermore, when MEL cells acquire the differentiated non-growing phenotype, the level of PKC-θ is reduced to less than 5%, suggesting that this PKC isoenzyme is no longer required. We propose that, unlike other members of the PKC family, PKC-θ may play a role in cell proliferation.