We report a linkage between cell aggressiveness, protein kinase C (PKC) activity, tyrosine kinase (PTK) activity and serum requirement. We used 2 leukemic cell lines induced by Moloney murine leukemia virus (MLV). One line was highly aggressive (BS‐24‐1) and required low serum concentrations (3%) for optimal growth in comparison to the less aggressive line (RO2T) that needed 10% serum for optimal growth. The more malignant cells exhibited higher PKC and PTK activity. This activity was independent of serum concentration between 0.01–10%. In contrast, the weakly malignant cells need a high serum concentration (10%) for optimal PKC or PTK activity. Immunoblot analysis revealed a higher level of PKC protein in the BS‐24‐1 cells than in the RO2T cells. Serum induction of PKC activity did not change the amount of PKC protein in the cytosol or the membrane fractions, indicating post‐translational mechanism regulation of PKC. We suggest that the aggressiveness of BS‐24‐1 resulted from its ability to become independent of growth regulation by serum factors, via autocrine stimulation of PKC and PTK.