The present invention relates to amino acid sequences that are directed against (as defined herein) G-protein coupled receptors (GPCRs) and in particular to CXCR4 and CXCR7, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences (also referred to herein as &ldquo；amino acid sequences of the invention&rdquo；, &ldquo；compounds of the invention&rdquo；, and &ldquo；polypeptides of the invention&rdquo；, respectively). Furthermore, the invention provides a new method of making amino acid sequences that are directed against transmembrane protein, and in particular for multiple spanning transmembrane proteins for which the native conformation cannot be reproduced in other &ldquo；in vitro&rdquo； system (e.g. GPCRs in general).
