In this study the effect of various Protein kinase C (PKC) aetivators/tumour promoters on the maturation and activity of human peripheral blood monocytes was examined. Monocytes were cultured in the absence or presence of various PKC activators for up to 2 weeks, and examined for the number of adherent cells, expression of myeloperoxidase enzymes, CDI4 antigens, mannose/N‐aeetylglucosamine (Man/GlcNAc) receptors, and the production ofTNF‐γ. The presence of PKC activators in cultures of monocyte‐derived macrophages (HuMoDM) prevented the loss in the number of initially plated monocytes, otherwise observed in long‐term tissue cultures with time of incubation. This effect of PKC activators on monocyte survival was diminished in the presence of PKC inhibitors. HuMoDM obtained in the presence ofPKC activators maintained a normal differentiation pattern, as was evident by the loss of granular myeloperoxidase enzytnes and CDI4 antigens, and the acquisition of metnbrane Man/GlcNAc receptors. HuMoDM which differentiated in the presence of PKC activators also released TNF‐γ in comparable amounts to freshly harvested human monoeytes. PKC activators/tumour promoters augmented the viability of long‐term cultures of human monoeyte‐derived macrophages. Such macrophages may facilitate cell and molecular biology studies of differentiated hu