Cellular sensitivity to cis‐diamminedichloroplatinum(II) (cDDP) can be regulated by protein kinase C (PKC) signal transduction pathway. Activators of PKC were shown to en‐ hance the sensitivity of human ovarian carcinoma 2008 cells to cDDP. We have examined whether or not the PKC signal transduction pathway is affected during‐development of resistance by tumor cells to cDDP. A 2‐fold decrease in PKC activity was observed in cDDP‐resistant ovarian carcinoma 2008 J. C13*5.25 cells compared with the drug‐sensitive 2008 cells. Subceflular distribution studies revealed a reduction in both cytosolic and paniculate PKC activities in 2008/C13*5.25 cells. The pattern of PKC isoform expression was compared in cDDP‐sensitive and ‐resistant cell lines by Western blot analysis with isoform‐specific antibodies to PKC. The parental cells expressed PKCα, ‐ε, and ‐ζ isoforms. The abundance of PKCα decreased significantly in 2008/C 13*5.25 cells, whereas the amount of PKCe increased moderately in the resistant variant, with no alteration in PKCε content. Therefore, a reduction in PKCa and/or an increase in PKCε expression may be associated with the drug‐resistant phenotype. © 1995 Wiley‐Liss, Inc.