To study the distribution and the degree of polymerization of actin in regenerating and neoplastic cells we have examined: (1) the immunofluorescent staining of these cells with human antiactin antibodies (AAA), (2) the sensitivity of cellular actin to AAA staining after treatment with the actin-depolymerizing factor present in plasma or serum of several animal species, and (3) the total and relative amounts of F- and G-actin in tissue preparations, determined by means of differential centrifugation and densitometric analysis of stained sodium dodecyl sulfate-polyacrylamide gels. There was little or no difference in staining intensity between normal and regenerating or tumoral tissues when treated with AAA, but AAA staining of normal tissues was abolished, whereas staining of regenerating and tumoral tissues remained intense after incubation with actin-depolymerizing factor. Gel analysis showed that normal, regenerating, and neoplastic epidermal cells contained similar amounts of actin. Compared to controls, regenerating liver tissue contained slightly more total actin, nearly the same amount of G-actin, but a substantially increased amount of F-actin. These results suggest that: (1) compared to controls, a greater proportion of regenerating and neoplastic tissue actin is stabilized against the action of actin-depolymerizing factor; (2) changes involving actin in regenerating and neoplastic epithelial cells reflect changes in its degree of polymerization rather than its total amount.