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A new way of assessing the significance of intracellular signals that may regulate cellular proliferation, would be to analyze possible 'second messengers' when proliferation is slowed down, rather than stimulated. Therefore, we examined proliferating mononuclear blood cells from leukaemic patients which had been exposed to an inhibitory ox leucocyte extract. The extract decreased H-thymidine incorporation in leukaemic cells in short-term cultures. The inhibition was not cell-line specific, but was nevertheless non-toxic and not due to endotoxin. The K flux into the leukaemic cells was assessed with Rb, a K analogue. An inverse relationship was found between Rb uptake and H-thymidine incorporation. The increased Rb influx was probably due to leakage or exchange mechanisms other than the Na/K membrane pump, as suggested by ouabain inhibition experiments. However, the long lag time (>45 min) between addition of inhibitor and a marked increase in Rb uptake does not support a role for the K flux as an early mediator of the inhibitory signal. [ABSTRACT FROM AUTHOR]