We investigated the possibility that human alpha-calcitonin-gene related peptide (CGRP)-(8-37) and human beta CGRP-(8-37) show some selectivity as antagonists of CGRP1 and CGRP2 receptor-mediated responses. Bindings assays showed that human alpha CGRP, human alpha CGRP-(8-37) and human beta CGRP-(8-37) showed high affinity (in the nanomolar concentration range) for CGRP receptors expressed in SK-N-MC cells and also in rat brain membrane preparations. Both human alpha CGRP-(8-37) and human beta CGRP-(8-37) were potent antagonists of human alpha CGRP-stimulated cAMP accumulation in SK-N-MC cells. However, both human alpha CGRP-(8-37) and human beta CGRP-(8-37) were weakly effective in antagonizing human alpha CGRP-stimulated responses in guinea-pig atria and rat vas deferens. In rat vas deferens, but not guinea-pig atria, the effects of human alpha CGRP and human alpha CGRP-(8-37) (but not human beta CGRP-(8-37)) were potentiated by thiorphan. Neither human alpha- nor human beta CGRP-(8-37) showed selectivity for supposedly CGRP1 and CGRP2 receptor-mediated responses. Furthermore, differences in the effects of the truncated CGRP analogues may reflect differences in enzyme distribution rather than the existence of CGRP receptor subtypes.