Protein kinase C (PKC) is a family of phospholipid-dependent kinases that is involved, along with calcium mobilization, in the activation of human platelets. Since interleukin-3 (IL-3) has been shown to act, in part, by activating PKC, we investigated the effect of IL-3 on PKC activity and content in human platelets. Exposure of platelets to 10 ng/ml of IL-3 was associated with a rapid (i.e., within 3 minutes) translocation of PKC activity and content from the cytosol to the membrane fraction. In addition, treatment with IL-3 effected a time-dependent down-regulation of PKC activity and content. We speculate that IL-3 may act as a modulator of PKC-dependent pathways in the human platelet.