Selected agonists convert the leukocyte integrin alpha M beta 2 on monocytes from a low to a high affinity state competent to bind factor X and fibrinogen. Conformational changes of alpha M beta 2 re hypothesized to account for this functional transition. Here we report that cytochalasins known to interfere with actin filaments induce the alpha M beta 2 functional transition. Upon exposure to cytochalasin B, isolated human blood monocytes and cells of the monocytic cell line THP-1 bound 125I-factor X (X) or 125I-fibrinogen (Fg) in a Ca(2+)-dependent, saturable manner. Monoclonal antibodies (mAbs) to the alpha M subunit and the common beta 2 subunit of leukocyte integrins inhibited X and Fg binding, whereas mAbs to the alpha chains of the other leukocyte integrins had no effect. Anti-alpha M mAb immunoprecipitated 125I-X that had been chemically cross-linked to its cognate receptor. Specific binding was not associated with an increased surface density of beta 2 integrins consistent with conformational remodeling of the receptor. Simultaneous analysis of actin forms in viable monocytes indicated a dynamic redistribution of cellular actin. The transient increase in G actin concurrent with an agonist action such as cytochalasin or ADP was reversed by an increase in F actin coincident with X/Ca2+ binding. A potential role of actin redistribution in alpha M beta 2 functional transition is supported by the finding that cells in which cellular actin is restricted to G rather than F form bound X and initiated a rapid coagulant response. We propose that a transient disassembly of actin filaments may relieve constraints on alpha M beta 2 via the cytoplasmic domains, permitting the conformational dynamics required for recognition of ligands.