The mechanism of cell shape changes and haematogenous translocations (metastases) in mouse malignant melanoma cells induced by phorbol esters and protein kinase C (PKC) is reported as adhesion “downregulation”, exocytosis and motility. However, PKC activation also produces intracellular alkalinization, a causal factor in plasma membrane internalization, cell rounding and detachment that does not necessarily implicate specific cell adhesion downregulation. We show here that Cloudman mouse malignant melanoma cells can be induced to round up and detach with concomitant intracellular alkalinization by simple inorganic sulphate treatment, thereby suggesting an alternative explanation to the reported phenomena, © 1993, Academic Press Limited. All rights reserved.