AbstractMacrophage Inflammatory Protein-1α(MIP-1α) can inhibit the proliferation of multipotent haemopoietic cells. Using the FDCP-Mix A4 multipotent stem cell line, MIP-1αwas shown to inhibit IL-3 stimulated cell cycling (assessed using the [3H]-thymidine“suicide”assay). Furthermore MIP-1αcan inhibit IL-3-stimulated [3H]-thymidine incorporation in FDCP-Mix cells, with half maximal inhibition observed at 3 ng/ml MIP-1α. Prostaglandin E2, but not MlP-1αwas able to elevate cyclic AMP levels in FDCP-Mix A4 cells although both agents can cause growth inhibition. However, MIP-1αaddition resulted in a pertussis-toxin-insensitive increase in the level of the second messenger inositol 1,4,5 trisphosphate (Ins 1,4,5P3). This response was both rapid (maximal at 5 seconds) and transient. A half maximal effect was observed at 5 ng/ml MIP-1αand the dose dependency correlated with that for MIP-1αmediated growth inhibition. A rapid increase in cytosolic Ca2+levels was also observed in response to MIP-1α. Inositol lipid hydrolysis and an increase in cytosolic Ca2+(signals normally associated with proliferation) may therefore be implicated in growth inhibitory mechanisms in multipotent cells.