Local anaesthetics are often applied directly onto the skin, and for this reason the effect of some local anaesthetics upon morphology and cytoskeleton organisation in human skin fibroblasts was investigated. In this paper the authors report that procaine (p-aminobenzoic acid diethylamino-etyl ester hydrochloride) induced vacuolisation of cytoplasm and great enhancement of neutral red accumulation in human skin fibroblasts cultured in vitro. Procaine-induced vacuolisation of cell's cytoplasm was observed to be associated with the enhanced uptake and inhibited release of fluid taken by endocytosis. All these effects appeared fully reversible. The cell vacuolisation cannot be prevented by 3-methyadenine, brefeldine A, and cytochalasine D. On the other hand, nocodazole and caffeine prevent cytoplasm vacuolisation induced by procaine. These observations suggest that procaine-induced formation of great vacuoles is due to an impairment of membrane traffic between endosomes. The authors' results also demonstrate that neutral red uptake assay, if used as a cell viability test, must be interpreted with great caution.