PURPOSE: To assess the in vivo evolution of argon laser retinal lesions by correlating the cross-sectional structure from sequential optical coherence tomography with histopathologic sectioning. METHODS: Argon laser lesions were created in the retinas of Macaca mulatta and evaluated by cross-section optical coherence tomography, which was compared at selected time points with corresponding histopathology. RESULTS: Argon laser lesions induced an optical coherence tomography pattern of early outer retinal relative high reflectivity with subsequent surrounding relative low reflectivity that correlated well with histopathologic findings. The in vivo optical coherence tomography images of macular laser lesions clearly demonstrated differences in pathologic response by retinal layer over time. CONCLUSION: The novel sequential imaging of rapidly evolving macular lesions with optical coherence tomography provides new insight into the patterns of acute tissue response by cross-sectional layer. This sequential imaging technique will aid in our understanding of the rapid evolution of retinal pathology and response to treatment in the research and clinical setting.