Relationships among the G-protein-coupled receptors were evaluated using several distance matrices with the neighbor-joining method of Saitou and Nei (1987). The relationships generated vary depending upon alignment, length, or region of sequence compared, and the distance matrix used to score similarity. To provide a statistical level of confidence, bootstrap resampling was applied to the analysis of a selection of G-protein-coupled receptors and the subfamily photoreceptor opsins. A general consensus indicates that the opsins behave as a discrete subfamily among the superfamily of G-protein-coupled receptors. Their relationship to other subfamilies remains unresolved. Within the opsin subfamily, the retinochromelike opsins segregate as a discrete group, but are more closely related to the invertebrate than vertebrate opsins. Among vertebrate opsins, the long wavelength cone opsins, the blue/violet opsins, and the rod opsins (including a class of green cone opsins) form distinct subgroups, but their relationships to one another remain unresolved. For this superfamily of receptors, the confidence levels for many branch pairings are low. The application of methods complimentary to those used in this preliminary study will be necessary to resolve questions about appropriate pairing and evolutionary relationships.