We have complemented multiple sequence alignments of the lectin domains of the selectins with an analysis of structurally invariant regions in X-ray structures of the mannose-binding protein (MBP) and E-selectin. The analysis shows that regions of structural conservation between MBP and E-selectin extend beyond regions of rigorous sequence conservation within the selectin family and suggests that reliable three-dimensional models of selectins from different species can be generated by modification of only a few backbone segments in E-selectin. A model of the L-selectin lectin domain is built and discussed with regard to observed differences in selectin specificity.