The viscoelastic properties of both hepatocytes and hepatocellular carcinoma (HCC) cells were measured by means of a micropipette aspiration technique. Experimental results were analyzed with a three-element standard linear solid model, in which an elastic element, K1, is in parallel with a Maxwell element composed of another elastic element, K2, in series with a viscous element, mu. Further, we investigated the relevance of viscoelastic properties of these two types of cells to the cytoskeleton structures by treating cells with three cytoskeletal perturbing agents, namely cytochalasin D (CD), colchicine (Col) and vinblastine (VBL). The results showed that the elastic coefficients, but not viscous coefficient of HCC cells (K1 = 103.6 +/- 12.6 N m-2, K2 = 42.5 +/- 10.4 N m-2, mu = 4.5 +/- 1.9 Pa s, n = 30), were significantly higher than the corresponding values for hepatocytes (K1 = 87.5 +/- 12.1 N m-2, K2 = 33.3 +/- 10.3 N m-2, mu = 5.9 +/- 3.0 Pa s, n = 24). Upon treatment with CD, the viscoelastic coefficients of both hepatocytes and HCC cells decreased uniformly, with magnitudes for the decrease in elastic coefficients of HCC cells (K1: 68.7 to 81.7 N m-2, 66.3 to 78.9%; K2: 34.5 to 37.1 N m-2, 81.2 to 87.3%) larger than those for normal hepatocytes (K1: 42.6 to 49.8 N m-2, 48.7 to 56.9%; K2: 17.2 to 20.4 N m-2, 51.7 to 61.3%). There was a smaller decrease in the viscous coefficient of HCC cells (2.0 to 3.4 Pa s, 44.4 to 75.6%) than that for hepatocytes (3.0 to 3.9 Pa s, 50.8 to 66.1%). Upon treatment with Col and VBL, the elastic coefficients of hepatocytes generally increased or tended to increase while those of HCC cells decreased. The differences in either the pattern or the magnitude of the effect of cytoskeletal perturbing agent on the viscoelastic properties between HCC cells and hepatocytes might possibly reflect differences in the state of the cytoskeleton structure and function, or in the cells' sensitivity to perturbing agent treatment between these two types of cells. Changes in the viscoelastic properties of cancer cells might well affect tumor cell invasion and metastasis as well as interactions between tumor cells and their micro-mechanical environments.