Leaf cytoarchitecture was evaluated by light microscopy and scanning electron microscopy, and cell viability was monitored by fluorescence after treatment of velvetleaf with defined concentrations and droplet sizes of formulated glyphosate and blended tallowamine surfactant. In response to droplets of formulated glyphosate larger than in field sprays but useful for studying structural change, we observe that the leaf epidermis thins and flattens within 1.5 h, the epidermal, mesophyll, and vascular cells at the contact site exhibit localized cytolysis by 6 h, and cytolysis and pycnosis remain restricted to the contact site at 24 h. Using endogeneous fluorescence as a marker for nonviable cells, it was determined that cellular changes are directly correlated with droplet size and that the changes are minimal after exposure to spray sizes and concentrations of formulated glyphosate and blended tallowamine typically used in the field. The results show that, at field use concentrations, the effect of formulated glyphosate and blended tallowamine on leaf cytoarchitecture is modest and localized but sufficient to allow herbicide entry.