The mechanism underlying type I angiotensin II (Ang II) receptor (AT1 receptor) desensitisation is unknown. Structural features suggest it may be a substrate for protein kinase C (PKC). The effects of a selective PKC inhibitor, Ro 31-7549, on receptor desensitisation were investigated in CHO cells expressing the human AT1 receptor. Desensitisation was demonstrated with respect to the calcium response to Ang II in Fura-2-loaded cells. Ro 31-7549 had no effect on desensitisation. However, pretreatment with Ro 31-7549 caused a dose-dependent reduction in calcium release from intracellular stores. PKC may therefore act at a locus distal from the receptor itself.