Protein kinase C (PKC), the mediator of the phosphoinositide transduction pathway, is a family of at feast 11 isozymes and its heterogeneity has been described in many tissues and cells. We studied here the heterogeneity of PKC in thyroid glands from three different species, rat, pig, and dog. By combining immunological and biochemical approaches, we identified in rat thyroids, the PKC alpha, beta II, delta, epsilon, and zeta subspecies, in pig thyroids, the alpha, epsilon, and zeta isozymes, and in dog thyroids, only the alpha and zeta isozymes. The observed species differences of the thyroid gland PKC heterogeneity could be related to the reported species differences in the activation of the phosphoinositide regulatory cascade by TSH and other thyroid cell regulators.