In many organs, different protein kinase C (PKC) isoforms are expressed in specific cell types, suggesting that the different PKCs have cell-specific roles, and also that drugs acting on a particular PKC may have effects on the whole organ that are distinguishable from drugs that target other isoforms. Previous studies of the guinea-pig and mouse intestine indicate that there are cell-specific expressions of PKC isoforms in neurons, muscle and the interstitial cells of Cajal. In the present study we have investigated the expression of different PKCs in human intestine. Immunohistochemical studies showed that the forms that are prominent in human enteric neurons are PKCs gamma and epsilon and in muscle the dominant form is PKCdelta. Neurons were weakly stained for PKCbetaI. These observations parallel findings in guinea-pig and mouse, except that in human PKCgamma-IR was not present in the same types of neurons that express it in the guinea-pig. Enteric glial cells were strongly immunoreactive for PKCalpha, which is also the major isoform in enteric glial cells of guinea-pig. In human and guinea-pig, glial cells also express PKCbetaI. Spindle-shaped cells in the mucosa were immunoreactive for PKCalpha and PKCgamma and in the muscle layers similar cells had PKCgamma-IR and PKCtheta-IR. The spindle-shaped cells were similar in morphology to interstitial cells of Cajal. Western analysis and RT-PCR confirmed the presence of the PKC isoform proteins and mRNA in the tissue. We conclude that there is cell-type specific expression of different PKCs in enteric neurons and intestinal muscle in human tissue, and that there are strong similarities in patterns of expression between laboratory animals and human, but some clear differences are also observed.