Thein vitrocytotoxicity of amosite asbestos and its silanized and bovine serum albumin conjugated derivatives were studied in two cell lines. The overall cytotoxicity of amosite towards Chinese hamster lung cells (V79–4) was not affected by derivatization, although the rate of cell‐particle interaction was reduced. Protein derivatization virtually abolished the cytolytic action of amosite to the macrophage‐like cell line (P388D1), although this derivatized material still induced the release of arachidonate. These results confirm that thein vitrocytotoxic effect of fibrous particulates toward V79–4 cells is mainly dependent on fiber size, while the response of macrophage‐like cells is more sensitive to alterations in surface chemistry. The relationship between these results and the pathogenicity of asbestos is discussed.