Electron microscopy and in vitro techniques were used to evaluate the morphologic responses of glomerular podocytes and glomerular endothelial cells to compounds that affect either cytoplasmic contractile elements or cytoplasmic microtubules. In response to in vitro incubation in the presence of cytochalasin D or B (compounds that inhibit contraction of actin-like microfilaments), podocyte foot processes change in shape from short processes with broad bases to taller processes with narrow bases. Coincident with these shape changes, there is an increase in the number of fully patent filtration slit spaces between adjacent foot processes. In view of these observations, it is proposed that glomerular podocytes have the potential for monitoring the filtration slit area available for solute efflux across the glomerular wall by modifying the shapes of their foot processes (that is, expanding and contracting the bases of these structures). As in vitro incubation continues for 1 to 2 days, the cytochalasins inhibit the shape changes of glomerular podocytes that normally occur during 2 days of in vitro incubation--the loss of foot processes, filtration slits, endothelial pores, and thickening of the endothelium. The cytochalasins also inhibit the loss of foot processes and filtration slits that otherwise occur in response to enzymatic removal of glomerular-free surface sialic acid. The in vitro depolymerization of glomerular microtubules by any of a variety of drugs (for example, vinblastine sulfate, colchicine) results in the rounding up of podocyte cell bodies, the thinning of podocyte major processes, and a partial collapsing of the glomerular endothelial walls. These latter observations suggest that microtubules play an important cytoskeletal role in maintaining the structural integrity of these cells.