In a previous study, we demonstrated that forced expression of a dominant-negative allele of Crx in developing rods blocked formation of both rod spherules in the outer plexiform layer (OPL) and outer segments [7]. To expand on these studies, the ultrastructure of photoreceptor synapses was examined in Crx-/- retinas. In Crx+/+ retinas at P21, newly mature rod spherules were abundant (Figure 7A). The sperules were blunt or club-shaped structures with a single ribbon associated with a single invaginating synapse (Figure 7A, arrow indicates one example; Figure 8A and 8B). Two processes from horizontal cells were situated on either side of the synaptic ridge (Figure 8B, labelled H) and one or more dendrites of rod bipolar cells occupied a central position (Figure 8B, bipolar labelled B). Cone terminals are large, flat pedicles that exhibit many invaginating synapses containing separate sets of horizontal and bipolar cell processes. Each pedicle contains numerous ribbons. These terminals were much less common than spherules in Crx+/+ retinas at P21 (Figure 7, box). In the OPL of Crx-/- retinas, photoreceptor terminals were highly disorganized at P21 (Figure 7B, arrows). Processes containing synaptic vesicles and ribbon-like structures were apparent, suggesting at least limited generation of synapse components. However, well formed spherules and pedicles were not observed. In addition, many terminals appeared to contain multiple ribbons (Figure 8C and 8D, r) not tethered to the plasma membrane and occasionally in perinuclear positions (Figure 8D).